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1. Severe enterovirus infections in patients with immune-mediated inflammatory diseases receiving anti-CD20 monoclonal antibodies

Author

Eric Hachulla, Alexis Mathian, Luc Mouthon, Bertrand Dunogue, Benjamin Terrier, Adrien Lemaignen, Fabienne Coury-Lucas, Virginie Rieu, Hélène Chaussade, Aurélie Ruet, Jerome Hadjadj, Gregoire Martin de Fremont, Maelle le Besnerais, Hélène Chabrolles, Audrey Mirand, Anne Sophie L'Honneur, Nicolas Mélé, David Boutboul, Meryem Farhat, Mouna Lazrek, Sonia Burrel, Isabelle Schuffenecker, Karl Stefic, Marion Carrette, and Veronique Avettand-Fenoel

Subjects
Medicine
Abstract

Objective Patients with X linked agammaglobulinemia are susceptible to enterovirus (EV) infections. Similarly, severe EV infections have been described in patients with impaired B-cell response following treatment with anti-CD20 monoclonal antibodies (mAbs), mostly in those treated for haematological malignancies. We aimed to describe severe EV infections in patients receiving anti-CD20 mAbs for immune-mediated inflammatory diseases (IMIDs).Methods Patients were included following a screening of data collected through the routine surveillance of EV infections coordinated by the National Reference Center and a review of the literature. Additionally, neutralising antibodies were assessed in a patient with chronic EV-A71 meningoencephalitis.Results Nine original and 17 previously published cases were retrieved. Meningoencephalitis (n=21/26, 81%) associated with EV-positive cerebrospinal fluid (n=20/22, 91%) was the most common manifestation. The mortality rate was high (27%). EV was the only causal agents in all reported cases. Patients received multiple anti-CD20 mAbs infusions (median 8 (5–10)), resulting in complete B-cell depletion and moderate hypogammaglobulinemia (median 4.9 g/L (4.3–6.7)), and had limited concomitant immunosuppressive treatments. Finally, in a patient with EV-A71 meningoencephalitis, a lack of B-cell response to EV was shown.Conclusion EV infection should be evoked in patients with IMIDs presenting with atypical organ involvement, especially meningoencephalitis. Anti-CD20 mAbs may lead to impaired B-cell response against EV, although an underlying primary immunodeficiency should systematically be discussed.

Published
2024
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2. Sudden Infant Death Associated with Rhinovirus Infection

Author

Christelle Auvray, Stéphanie Perez-Martin, Isabelle Schuffenecker, Cécile Pitoiset, Georges Tarris, Katia Ambert-Balay, Laurent Martin, Nathalie Dullier-Taillefumier, Jean-Baptiste Bour, and Catherine Manoha

Subjects
infant, sudden death, rhinovirus, cerebrospinal fluid, fatal, virus, Microbiology, QR1-502
Abstract

A less than one-month-old infant with symptoms of rhinitis died unexpectedly in his sleep. He was not born prematurely and had no known underlying disease. Cerebrospinal fluid, nasopharyngeal and lung samples, and rectal swab were found to be positive for subgroup A rhinovirus, while the blood was negative. This case highlights the important finding that the rhinovirus, a common pathogen associated with upper respiratory tract infections, can sometimes, as the only pathogen, lead to complications such as a cerebrospinal infection and be involved in the sudden infant death syndrome (SIDS). Vigilance is necessary in case of viral infections in the infant’s environment, and measures of hygiene and protection must be encouraged in order to reduce the risk of the SIDS.

Published
2024
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3. Molecular Epidemiology and Evolutionary Trajectory of Emerging Echovirus 30, Europe

Author

Kimberley S.M. Benschop, Eeva K. Broberg, Emma Hodcroft, Dennis Schmitz, Jan Albert, Anda Baicus, Jean-Luc Bailly, Gudrun Baldvinsdottir, Natasa Berginc, Soile Blomqvist, Sindy Böttcher, Mia Brytting, Erika Bujaki, Maria Cabrerizo, Cristina Celma, Ondrej Cinek, Eric C.J. Claas, Jeroen Cremer, Jonathan Dean, Jennifer L. Dembinski, Iryna Demchyshyna, Sabine Diedrich, Susanne Dudman, Jake Dunning, Robert Dyrdak, Mary Emmanouil, Agnes Farkas, Cillian De Gascun, Guillaume Fournier, Irina Georgieva, Ruben Gonzalez-Sanz, Jolanda van Hooydonk-Elving, Anne J. Jääskeläinen, Ruta Jancauskaite, Kathrin Keeren, Thea K. Fischer, Sidsel Krokstad, Lubomira Nikolaeva–Glomb, Ludmila Novakova, Sofie E. Midgley, Audrey Mirand, Richard Molenkamp, Ursula Morley, Joël Mossong, Svajune Muralyte, Jean-Luc Murk, Trung Nguyen, Svein A. Nordbø, Riikka Österback, Suzan Pas, Laura Pellegrinelli, Vassiliki Pogka, Birgit Prochazka, Petra Rainetova, Marc Van Ranst, Lieuwe Roorda, Isabelle Schuffenecker, Rob Schuurman, Asya Stoyanova, Kate Templeton, Jaco J. Verweij, Androniki Voulgari-Kokota, Tytti Vuorinen, Elke Wollants, Katja C. Wolthers, Katherina Zakikhany, Richard Neher, Heli Harvala, and Peter Simmonds

Subjects
Molecular epidemiology, evolutionary trajectory, epidemiological monitoring, whole-genome sequencing, genetic recombination, neurological manifestations, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

In 2018, an upsurge in echovirus 30 (E30) infections was reported in Europe. We conducted a large-scale epidemiologic and evolutionary study of 1,329 E30 strains collected in 22 countries in Europe during 2016–2018. Most E30 cases affected persons 0–4 years of age (29%) and 25–34 years of age (27%). Sequences were divided into 6 genetic clades (G1–G6). Most (53%) sequences belonged to G1, followed by G6 (23%), G2 (17%), G4 (4%), G3 (0.3%), and G5 (0.2%). Each clade encompassed unique individual recombinant forms; G1 and G4 displayed >2 unique recombinant forms. Rapid turnover of new clades and recombinant forms occurred over time. Clades G1 and G6 dominated in 2018, suggesting the E30 upsurge was caused by emergence of 2 distinct clades circulating in Europe. Investigation into the mechanisms behind the rapid turnover of E30 is crucial for clarifying the epidemiology and evolution of these enterovirus infections.

Published
2021
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4. Severe Acute Flaccid Myelitis Associated With Enterovirus in Children: Two Phenotypes for Two Evolution Profiles?

Author

Melodie Aubart, Cyril Gitiaux, Charles Joris Roux, Raphael Levy, Isabelle Schuffenecker, Audrey Mirand, Nathalie Bach, Florence Moulin, Jean Bergounioux, Marianne Leruez-Ville, Flore Rozenberg, Delphine Sterlin, Lucile Musset, Denise Antona, Nathalie Boddaert, Shen Ying Zhang, Manoelle Kossorotoff, and Isabelle Desguerre

Subjects
enterovirus, myelitis, children, EV-D68, EV-A71, Neurology. Diseases of the nervous system, RC346-429
Abstract

Acute flaccid myelitis (AFM) is an acute paralysis syndrome defined by a specific inflammation of the anterior horn cells of the spinal cord. From 2014, worrying waves of life-threatening AFM consecutive to enterovirus infection (EV-D68 and EV-A71) have been reported. We describe 10 children displaying an AFM with an EV infection, the treatments performed and the 1 to 3-years follow-up. Two groups of patients were distinguished: 6 children (“polio-like group”) had severe motor disability whereas 4 other children (“brainstem group”) displayed severe brainstem weakness requiring ventilation support. Electrodiagnostic studies (n = 8) support the presence of a motor neuronopathy associated to myelitis. The best prognosis factor seems to be the motor recovery after the first 4 weeks of the disease.

Published
2020
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5. Analytical Performances of the Panther Fusion System for the Detection of Respiratory Viruses in the French National Reference Centre of Lyon, France

Author

Maxime Pichon, Martine Valette, Isabelle Schuffenecker, Geneviève Billaud, and Bruno Lina

Subjects
respiratory viruses, influenza, diagnostic PCR, performance evaluation, automation, respiratory tract samples, Biology (General), QH301-705.5
Abstract

Respiratory infection are mainly caused by viral pathogens. During the 2017–2018 epidemic season, Panther Fusion® Respiratory kits (Influenza virus A&B (FluA&B), respiratory syncytial virus (RSV), adenovirus (ADV), metapneumovirus (MPV), rhinovirus (RV), parainfluenzae virus (PIV), were compared to the Respiratory MultiWells System r-gene. Respiratory clinical specimens were tested retrospectively (n = 268) and prospectively (n = 463). Analytical performances were determined (sensitivity –Sep-, specificity –Spe- and κ) considering concordances of ≥2 molecular testing specific to each viral target (discrepant results were verified at the National Reference Centres for Enteroviruses or Respiratory viruses, Lyon, France). After retrospective (and prospective) testing, Sep, Spe, and κ were 100% (97.7%), 100% (99%) and 100% (94%) for FluA: 100% (95.5%), 100% (99.3%) and 100% (94%) for FluB, and 100% (88.5%), 100% (98.7%) and 100% (89%) for RSV; 82.1% (41.7%), 100% (99.5%) and 86% (54%) for ADV; 94.7% (73.7%), 96.1% (98.0%) and 91% (65%) for MPV; 96.1% (94.6%), 90.2% (98.5%) and 86% (91%) for HRV; and 90% (72.7%), 100% (99.3%) and 91% (72%), respectively, for PIV. Analytical performances were above 85% for all viruses except for ADV, MPV and PIV, confirming the analytical performance of the Panther Fusion system, a high throughput system with reduced turn-around-time, when compared to non-automated systems.

Published
2020
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6. Risk Assessment and Virological Monitoring Following an Accidental Exposure to Concentrated Sabin Poliovirus Type 3 in France, November 2018

Author

Marion Jeannoël, Denise Antona, Clément Lazarus, Bruno Lina, and Isabelle Schuffenecker

Subjects
poliovirus, incident, accident, risk assessment, containment breach, GAP III, Medicine
Abstract

The safe and secure containment of infectious poliovirus (PV) in facilities where live PV are handled is the condition to achieve and maintain poliomyelitis eradication. Despite precautions to minimize the risk of release of PV from such facilities to the environment, breaches of containment have already been documented. Here, we report the management of an incident that occurred on 30 November 2018 in a French vaccine manufacturing plant. Five adequately vaccinated operators were exposed to a Sabin poliovirus type 3 (PV3) spill. A microbiological risk assessment was conducted and the operators were monitored for PV shedding. On day 5 after exposure, Sabin PV3 was detected only in the stool sample of the most exposed worker. Shedding of Sabin PV3 (as detected by viral culture) was restricted to a very short period (less than 15 days). Monitoring of this incident was an opportunity to assess the relevance of our national response plan. We concluded that the measures undertaken and reported here were appropriate and proportional.

Published
2020
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7. New Introductions of Enterovirus 71 Subgenogroup C4 Strains, France, 2012

Author

Isabelle Schuffenecker, Cécile Henquell, Audrey Mirand, Marianne Coste-Burel, Stéphanie Marque-Juillet, Delphine Desbois, Gisèle Lagathu, Laure Bornebusch, Jean-Luc Bailly, and Bruno Lina

Subjects
enterovirus 71, enterovirus species A, subgenogroup C4, Picornaviridae, France, viruses, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

In France during 2012, human enterovirus 71 (EV-A71) subgenogroup C4 strains were detected in 4 children hospitalized for neonatal fever or meningitis. Phylogenetic analysis showed novel and independent EV-A71 introductions, presumably from China, and suggested circulation of C4 strains throughout France. This observation emphasizes the need for monitoring EV-A71 infections in Europe.

Published
2014
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8. Fatal Case of Enterovirus 71 Infection, France, 2007

Author

Sophie Vallet, Marie-Christine Legrand-Quillien, Thomas Dailland, Gaëtan Podeur, Stéphanie Gouriou, Isabelle Schuffenecker, Christopher Payan, and Pascale Marcorelles

Subjects
Enterovirus 71, pulmonary edema, encephalitis, viruses, France, dispatch, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

A fatal case of enterovirus 71 infection with pulmonary edema and rhombencephalitis occurred in Brest, France, in April 2007. The virus was identified as subgenogroup C2. This highly neurotropic enterovirus merits specific surveillance outside the Asia-Pacific region.

Published
2009
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9. West Nile Virus in Morocco, 2003

Author

Isabelle Schuffenecker, Christophe N. Peyrefitte, Mohammed el Harrak, Séverine Murri, Agnès Leblond, and Hervé G. Zeller

Subjects
dispatch, West Nile, Morocco, phylogenetic analysis, equine encephalitis, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

West Nile virus (WNV) reemerged in Morocco in September 2003, causing an equine outbreak. A WNV strain isolated from a brain biopsy was completely sequenced. On the basis of phylogenetic analyses, Moroccan WNV strains isolated during the 1996 and 2003 outbreaks were closely related to other strains responsible for equine outbreaks in the western Mediterranean basin.

Published
2005
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11. Prospective study of Chikungunya virus acute infection in the Island of La Réunion during the 2005-2006 outbreak.

Author

Frederik Staikowsky, François Talarmin, Philippe Grivard, Abdel Souab, Isabelle Schuffenecker, Karin Le Roux, Marc Lecuit, and Alain Michault

Subjects
Medicine, Science
Abstract

BACKGROUND:Chikungunya virus (CHIKV) is a recently re-emerged arthropod borne virus responsible for a massive outbreak in the Indian Ocean and India, and extended to Southeast Asia as well as Italy. CHIKV has adapted to Aedes albopictus, an anthropophilic mosquito species widely distributed in Asia, Europe, Africa and America. Our objective was to determine the clinical and biological features of patients at the acute phase of CHIKV infection. METHODS AND FINDINGS:A prospective study enrolled 274 consecutive patients with febrile arthralgia recorded at the Emergency Department of the Groupe Hospitalier Sud-Réunion between March and May 2006. Three groups were defined: one group of 180 viremic patients (positive CHIKV RT-PCR), one group of 34 patients with acute post-viremic infection (negative CHIKV RT-PCR, positive anti-CHIKV IgM and negative IgG), and one group of 46 uninfected patients (negative CHIKV RT-PCR, anti-CHIKV IgM and IgG). Bivariate analyses of clinical and biological features between groups were performed. Patients with CHIKV viremia presented typically with asymmetrical bilateral polyarthralgia (96.5%) affecting the lower (98%) and small joints (74.8%), as well as asthenia (88.6%), headache (70%), digestive trouble (63.3%), myalgia (59%), exanthems (47.8%), conjunctival hyperhemia (23%) and adenopathy (8.9%). Vertigo, cutaneous dysesthesia, pharyngitis and haemorrhages were seldom observed. So far unreported symptoms such as chondrocostal arthralgia (20%), entesopathies (1.6%), talalgia (14%) were also noted. Prurit was less frequent during the viremic than post-viremic phase (13.9% vs. 41.2%; p

Published
2009
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12. Multidisciplinary prospective study of mother-to-child chikungunya virus infections on the island of La Réunion.

Author

Patrick Gérardin, Georges Barau, Alain Michault, Marc Bintner, Hanitra Randrianaivo, Ghassan Choker, Yann Lenglet, Yasmina Touret, Anne Bouveret, Philippe Grivard, Karin Le Roux, Séverine Blanc, Isabelle Schuffenecker, Thérèse Couderc, Fernando Arenzana-Seisdedos, Marc Lecuit, and Pierre-Yves Robillard

Subjects
Medicine
Abstract

BackgroundAn outbreak of chikungunya virus affected over one-third of the population of La Réunion Island between March 2005 and December 2006. In June 2005, we identified the first case of mother-to-child chikungunya virus transmission at the Groupe Hospitalier Sud-Réunion level-3 maternity department. The goal of this prospective study was to characterize the epidemiological, clinical, biological, and radiological features and outcomes of all the cases of vertically transmitted chikungunya infections recorded at our institution during this outbreak.Methods and findingsOver 22 mo, 7,504 women delivered 7,629 viable neonates; 678 (9.0%) of these parturient women were infected (positive RT-PCR or IgM serology) during antepartum, and 61 (0.8%) in pre- or intrapartum. With the exception of three early fetal deaths, vertical transmission was exclusively observed in near-term deliveries (median duration of gestation: 38 wk, range 35-40 wk) in the context of intrapartum viremia (19 cases of vertical transmission out of 39 women with intrapartum viremia, prevalence rate 0.25%, vertical transmission rate 48.7%). Cesarean section had no protective effect on transmission. All infected neonates were asymptomatic at birth, and median onset of neonatal disease was 4 d (range 3-7 d). Pain, prostration, and fever were present in 100% of cases and thrombocytopenia in 89%. Severe illness was observed in ten cases (52.6%) and mainly consisted of encephalopathy (n = 9; 90%). These nine children had pathologic MRI findings (brain swelling, n = 9; cerebral hemorrhages, n = 2), and four evolved towards persistent disabilities.ConclusionsMother-to-child chikungunya virus transmission is frequent in the context of intrapartum maternal viremia, and often leads to severe neonatal infection. Chikungunya represents a substantial risk for neonates born to viremic parturients that should be taken into account by clinicians and public health authorities in the event of a chikungunya outbreak.

Published
2008
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13. A mouse model for Chikungunya: young age and inefficient type-I interferon signaling are risk factors for severe disease.

Author

Thérèse Couderc, Fabrice Chrétien, Clémentine Schilte, Olivier Disson, Madly Brigitte, Florence Guivel-Benhassine, Yasmina Touret, Georges Barau, Nadège Cayet, Isabelle Schuffenecker, Philippe Desprès, Fernando Arenzana-Seisdedos, Alain Michault, Matthew L Albert, and Marc Lecuit

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

Chikungunya virus (CHIKV) is a re-emerging arbovirus responsible for a massive outbreak currently afflicting the Indian Ocean region and India. Infection from CHIKV typically induces a mild disease in humans, characterized by fever, myalgia, arthralgia, and rash. Cases of severe CHIKV infection involving the central nervous system (CNS) have recently been described in neonates as well as in adults with underlying conditions. The pathophysiology of CHIKV infection and the basis for disease severity are unknown. To address these critical issues, we have developed an animal model of CHIKV infection. We show here that whereas wild type (WT) adult mice are resistant to CHIKV infection, WT mouse neonates are susceptible and neonatal disease severity is age-dependent. Adult mice with a partially (IFN-alpha/betaR(+/-)) or totally (IFN-alpha/betaR(-/-)) abrogated type-I IFN pathway develop a mild or severe infection, respectively. In mice with a mild infection, after a burst of viral replication in the liver, CHIKV primarily targets muscle, joint, and skin fibroblasts, a cell and tissue tropism similar to that observed in biopsy samples of CHIKV-infected humans. In case of severe infections, CHIKV also disseminates to other tissues including the CNS, where it specifically targets the choroid plexuses and the leptomeninges. Together, these data indicate that CHIKV-associated symptoms match viral tissue and cell tropisms, and demonstrate that the fibroblast is a predominant target cell of CHIKV. These data also identify the neonatal phase and inefficient type-I IFN signaling as risk factors for severe CHIKV-associated disease. The development of a permissive small animal model will expedite the testing of future vaccines and therapeutic candidates.

Published
2008
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14. Two Chikungunya isolates from the outbreak of La Reunion (Indian Ocean) exhibit different patterns of infection in the mosquito, Aedes albopictus.

Author

Marie Vazeille, Sara Moutailler, Daniel Coudrier, Claudine Rousseaux, Huot Khun, Michel Huerre, Julien Thiria, Jean-Sébastien Dehecq, Didier Fontenille, Isabelle Schuffenecker, Philippe Despres, and Anna-Bella Failloux

Subjects
Medicine, Science
Abstract

BackgroundA Chikungunya (CHIK) outbreak hit La Réunion Island in 2005-2006. The implicated vector was Aedes albopictus. Here, we present the first study on the susceptibility of Ae. albopictus populations to sympatric CHIKV isolates from La Réunion Island and compare it to other virus/vector combinations.Methodology and findingsWe orally infected 8 Ae. albopictus collections from La Réunion and 3 from Mayotte collected in March 2006 with two Chikungunya virus (CHIKV) from La Réunion: (i) strain 05.115 collected in June 2005 with an Alanine at the position 226 of the glycoprotein E1 and (ii) strain 06.21 collected in November 2005 with a substitution A226V. Two other CHIKV isolates and four additional mosquito strains/species were also tested. The viral titer of the infectious blood-meal was 10(7) plaque forming units (pfu)/mL. Dissemination rates were assessed by immunofluorescent staining on head squashes of surviving females 14 days after infection. Rates were at least two times higher with CHIKV 06.21 compared to CHIKV 05.115. In addition, 10 individuals were analyzed every day by quantitative RT-PCR. Viral RNA was quantified on (i) whole females and (ii) midguts and salivary glands of infected females. When comparing profiles, CHIKV 06.21 produced nearly 2 log more viral RNA copies than CHIKV 05.115. Furthermore, females infected with CHIKV 05.115 could be divided in two categories: weakly susceptible or strongly susceptible, comparable to those infected by CHIKV 06.21. Histological analysis detected the presence of CHIKV in salivary glands two days after infection. In addition, Ae. albopictus from La Réunion was as efficient vector as Ae. aegypti and Ae. albopictus from Vietnam when infected with the CHIKV 06.21.ConclusionsOur findings support the hypothesis that the CHIK outbreak in La Réunion Island was due to a highly competent vector Ae. albopictus which allowed an efficient replication and dissemination of CHIKV 06.21.

Published
2007
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15. Characterization of reemerging chikungunya virus.

Author

Marion Sourisseau, Clémentine Schilte, Nicoletta Casartelli, Céline Trouillet, Florence Guivel-Benhassine, Dominika Rudnicka, Nathalie Sol-Foulon, Karin Le Roux, Marie-Christine Prevost, Hafida Fsihi, Marie-Pascale Frenkiel, Fabien Blanchet, Philippe V Afonso, Pierre-Emmanuel Ceccaldi, Simona Ozden, Antoine Gessain, Isabelle Schuffenecker, Bruno Verhasselt, Alessia Zamborlini, Ali Saïb, Felix A Rey, Fernando Arenzana-Seisdedos, Philippe Desprès, Alain Michault, Matthew L Albert, and Olivier Schwartz

Subjects
Immunologic diseases. Allergy, RC581-607, Biology (General), QH301-705.5
Abstract

An unprecedented epidemic of chikungunya virus (CHIKV) infection recently started in countries of the Indian Ocean area, causing an acute and painful syndrome with strong fever, asthenia, skin rash, polyarthritis, and lethal cases of encephalitis. The basis for chikungunya disease and the tropism of CHIKV remain unknown. Here, we describe the replication characteristics of recent clinical CHIKV strains. Human epithelial and endothelial cells, primary fibroblasts and, to a lesser extent, monocyte-derived macrophages, were susceptible to infection and allowed viral production. In contrast, CHIKV did not replicate in lymphoid and monocytoid cell lines, primary lymphocytes and monocytes, or monocyte-derived dendritic cells. CHIKV replication was cytopathic and associated with an induction of apoptosis in infected cells. Chloroquine, bafilomycin-A1, and short hairpin RNAs against dynamin-2 inhibited viral production, indicating that viral entry occurs through pH-dependent endocytosis. CHIKV was highly sensitive to the antiviral activity of type I and II interferons. These results provide a general insight into the interaction between CHIKV and its mammalian host.

Published
2007
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16. Genome microevolution of chikungunya viruses causing the Indian Ocean outbreak.

Author

Isabelle Schuffenecker, Isabelle Iteman, Alain Michault, Séverine Murri, Lionel Frangeul, Marie-Christine Vaney, Rachel Lavenir, Nathalie Pardigon, Jean-Marc Reynes, François Pettinelli, Leon Biscornet, Laure Diancourt, Stéphanie Michel, Stéphane Duquerroy, Ghislaine Guigon, Marie-Pascale Frenkiel, Anne-Claire Bréhin, Nadège Cubito, Philippe Desprès, Frank Kunst, Félix A Rey, Hervé Zeller, and Sylvain Brisse

Subjects
Medicine
Abstract

BackgroundA chikungunya virus outbreak of unprecedented magnitude is currently ongoing in Indian Ocean territories. In Réunion Island, this alphavirus has already infected about one-third of the human population. The main clinical symptom of the disease is a painful and invalidating poly-arthralgia. Besides the arthralgic form, 123 patients with a confirmed chikungunya infection have developed severe clinical signs, i.e., neurological signs or fulminant hepatitis.Methods and findingsWe report the nearly complete genome sequence of six selected viral isolates (isolated from five sera and one cerebrospinal fluid), along with partial sequences of glycoprotein E1 from a total of 127 patients from Réunion, Seychelles, Mauritius, Madagascar, and Mayotte islands. Our results indicate that the outbreak was initiated by a strain related to East-African isolates, from which viral variants have evolved following a traceable microevolution history. Unique molecular features of the outbreak isolates were identified. Notably, in the region coding for the non-structural proteins, ten amino acid changes were found, four of which were located in alphavirus-conserved positions of nsP2 (which contains helicase, protease, and RNA triphosphatase activities) and of the polymerase nsP4. The sole isolate obtained from the cerebrospinal fluid showed unique changes in nsP1 (T301I), nsP2 (Y642N), and nsP3 (E460 deletion), not obtained from isolates from sera. In the structural proteins region, two noteworthy changes (A226V and D284E) were observed in the membrane fusion glycoprotein E1. Homology 3D modelling allowed mapping of these two changes to regions that are important for membrane fusion and virion assembly. Change E1-A226V was absent in the initial strains but was observed in >90% of subsequent viral sequences from Réunion, denoting evolutionary success possibly due to adaptation to the mosquito vector.ConclusionsThe unique molecular features of the analyzed Indian Ocean isolates of chikungunya virus demonstrate their high evolutionary potential and suggest possible clues for understanding the atypical magnitude and virulence of this outbreak.

Published
2006
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17. Tickborne Encephalitis, Southwestern France

Author

Bruno Herpe, Isabelle Schuffenecker, Jérome Pillot, Denis Malvy, Benjamin Clouzeau, Nam Bui, Frederic Vargas, Didier Gruson, Hervé Zeller, Marie E. Lafon, Hervé Fleury, and Gilles Hilbert

Subjects
Tickborne encephalitis, arbovirosis, southwestern France, dispatch, France, Medicine, Infectious and parasitic diseases, RC109-216
Abstract

We report an autochthonous human case of tickborne encephalitis (TBE) in the Bordeaux area, southwestern France. The patient was a farmer who had severe encephalomyelitis. ELISA and neutralization assay of serum and cerebrospinal fluid established the diagnosis. This potential new endemic focus for TBE virus should be further investigated.

Published
2007
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18. Severe Acute Flaccid Myelitis Associated With Enterovirus in Children: Two Phenotypes for Two Evolution Profiles?

Author

Delphine Sterlin, Charles Joris Roux, Flore Rozenberg, Mélodie Aubart, Florence Moulin, Isabelle Schuffenecker, Audrey Mirand, Nathalie Boddaert, Cyril Gitiaux, Marianne Leruez-Ville, Shen-Ying Zhang, Nathalie Bach, Manoelle Kossorotoff, Isabelle Desguerre, Denise Antona, Raphael Levy, Lucile Musset, Jean Bergounioux, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Hôpital Raymond Poincaré [AP-HP], Hôpital Cochin [AP-HP], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), and Bailly, Jean-Luc

Subjects
Pediatrics, medicine.medical_specialty, Weakness, [SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, Myelitis, macromolecular substances, medicine.disease_cause, lcsh:RC346-429, 03 medical and health sciences, myelitis, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, 0302 clinical medicine, Anterior Horn Cell, children, EV-D68, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, 030212 general & internal medicine, lcsh:Neurology. Diseases of the nervous system, Original Research, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, business.industry, enterovirus, [SDV.NEU.NB] Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology, medicine.disease, Spinal cord, Acute flaccid myelitis, 3. Good health, Poliomyelitis, EV-A71, medicine.anatomical_structure, Neurology, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Enterovirus, Neurology (clinical), Brainstem, medicine.symptom, business, 030217 neurology & neurosurgery
Abstract

International audience; Acute flaccid myelitis (AFM) is an acute paralysis syndrome defined by a specific inflammation of the anterior horn cells of the spinal cord. From 2014, worrying waves of life-threatening AFM consecutive to enterovirus infection (EV-D68 and EV-A71) have been reported. We describe 10 children displaying an AFM with an EV infection, the treatments performed and the 1 to 3-years follow-up. Two groups of patients were distinguished: 6 children (“polio-like group”) had severe motor disability whereas 4 other children (“brainstem group”) displayed severe brainstem weakness requiring ventilation support. Electrodiagnostic studies (n = 8) support the presence of a motor neuronopathy associated to myelitis. The best prognosis factor seems to be the motor recovery after the first 4 weeks of the disease.

Published
2020
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19. Emergence of enterovirus D68 clade D1, France, August to November 2018

Author

Laurence Josset, Antonin Bal, Karen Brengel-Pesce, Thierry Wirth, Karl Stefic, F. Morfin, Marianne Coste-Burel, Bruno Lina, Mouna Lazrek, Marina Sabatier, Isabelle Schuffenecker, Centre National de Référence des Entérovirus, Hospices Civils de Lyon (HCL), Laboratoire de Virologie [HCL, Lyon] (Institut des Agents Infectieux), Hospices civils de Lyon (HCL)-HCL Groupement Hospitalier Nord [Lyon]-Centre National de Reference des virus des Infections Respiratoires France Sud [HCL, Lyon], Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), BIOMERIEUX, Institut de Systématique, Evolution, Biodiversité (ISYEB ), Muséum national d'Histoire naturelle (MNHN)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS)-Université des Antilles (UA), Service de virologie [CHU Nantes], Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Virologie [Lille], Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de bactériologie-virologie [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau, Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Muséum national d'Histoire naturelle (MNHN)-École pratique des hautes études (EPHE), Hôpital Bretonneau-Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), and Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)

Subjects
0301 basic medicine, Male, Epidemiology, Genetic analysis, Communicable Diseases, Emerging, Disease Outbreaks, respiratory infection, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Genotype, Clade, Child, Respiratory Tract Infections, Phylogeny, Aged, 80 and over, Enterovirus D, Human, whole genome sequencing, Respiratory infection, Middle Aged, 3. Good health, Child, Preschool, Population Surveillance, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, France, Rapid Communication, Adult, medicine.medical_specialty, Adolescent, 030106 microbiology, Biology, 03 medical and health sciences, Young Adult, Virology, medicine, Enterovirus Infections, Humans, emergence, Aged, metagenomics, outbreak, Public Health, Environmental and Occupational Health, Outbreak, Infant, enterovirus D68, Sequence Analysis, DNA, Genetic divergence, Molecular Typing, 030104 developmental biology, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Enterovirus D68
Abstract

International audience; We report a seasonal increase of enterovirus D68 (EV-D68) cases in France, with 54 cases detected between 19 August and 14 November 2018. Molecular typing revealed that 20 of 32 of the isolates belonged to clade D1, only sporadically detected before in France. Median age of D1-cases was 42 years, 10 developed severe respiratory signs and one had neurological complications. The 2018-D1 viruses showed a genetic divergence of 3.34 % with D1 viruses identified previously.

Published
2019
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20. Quality control implementation for universal characterization of DNA and RNA viruses in clinical respiratory samples using single metagenomic next-generation sequencing workflow

Author

Laurence Josset, Maxime Pichon, Florence Morfin, Martine Valette, Gaelle Vilchez, Bruno Lina, Sophie Trouillet-Assant, Jean-Sébastien Casalegno, Isabelle Schuffenecker, Guy Oriol, Caroline Picard, Lisa Billard, Antonin Bal, Karen Brengel-Pesce, Valérie Cheynet, Sophie Vallet, Yves Gillet, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre National de Reference des virus des Infections Respiratoires France Sud [HCL, Lyon], Biomérieux Lyon, BIOMERIEUX, Laboratoire de Virologie, Hospices Civils de Lyon (HCL), Virpath-Grippe, de l'émergence au contrôle -- Virpath-Influenza, from emergence to control (Virpath), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP), Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), EFS-Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO), Hôpital de la Cavale Blanche - CHRU Brest (CHU - BREST ), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), French foundation of innovation in infectious diseases, Bodescot, Myriam, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Institut Brestois Santé Agro Matière (IBSAM), and Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM)

Subjects
0301 basic medicine, medicine.medical_specialty, Viral metagenomics, Computational biology, Biology, Real-Time Polymerase Chain Reaction, Genome, DNA sequencing, lcsh:Infectious and parasitic diseases, 03 medical and health sciences, chemistry.chemical_compound, Medical microbiology, [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], medicine, Humans, RNA Viruses, lcsh:RC109-216, Respiratory Tract Infections, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, Respiratory samples, 030304 developmental biology, 0303 health sciences, Respiratory viruses, Clinical virology, 030306 microbiology, DNA Viruses, High-Throughput Nucleotide Sequencing, RNA, Quality control, 030104 developmental biology, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Workflow, Parasitology, Technical Advance, chemistry, Metagenomics, DNA, Viral, Next-generation sequencing, RNA, Viral, [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Genomics [q-bio.GN], DNA, SsDNA viruses
Abstract

BackgroundIn recent years, metagenomic Next-Generation Sequencing (mNGS) has increasingly been used for an accurate assumption-free virological diagnosis. However, the systematic workflow evaluation on clinical respiratory samples and implementation of quality controls (QCs) is still lacking.MethodsA total of 3 QCs were implemented and processed through the whole mNGS workflow: a notemplate-control to evaluate contamination issues during the process; an internal and an external QC to check the integrity of the reagents, equipment, the presence of inhibitors, and to allow the validation of results for each sample. The workflow was then evaluated on 37 clinical respiratory samples from patients with acute respiratory infections previously tested for a broad panel of viruses using semi-quantitative real-time PCR assays (28 positive samples including 6 multiple viral infections; 9 negative samples). Selected specimens included nasopharyngeal swabs (n = 20), aspirates (n = 10), or sputums (n = 7).ResultsThe optimal spiking level of the internal QC was first determined in order to be sufficiently detected without overconsumption of sequencing reads. According to QC validation criteria, mNGS results were validated for 34/37 selected samples. For valid samples, viral genotypes were accurately determined for 36/36 viruses detected with PCR (viral genome coverage ranged from 0.6% to 100%, median = 67.7%). This mNGS workflow allowed the detection of DNA and RNA viruses up to a semi-quantitative PCR Ct value of 36. The six multiple viral infections involving 2 to 4 viruses were also fully characterized. A strong correlation between results of mNGS and real-time PCR was obtained for each type of viral genome (R2 ranged from 0.72 for linear single-stranded (ss) RNA viruses to 0.98 for linear ssDNA viruses).ConclusionsAlthough the potential of mNGS technology is very promising, further evaluation studies are urgently needed for its routine clinical use within a reasonable timeframe. The approach described herein is crucial to bring standardization and to ensure the quality of the generated sequences in clinical setting. We provide an easy-to-use single protocol successfully evaluated for the characterization of a broad and representative panel of DNA and RNA respiratory viruses in various types of clinical samples.

Published
2018
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21. A Transmissible Rash of Palms and Soles in a 58-Year-Old Man

Author

Olivier Lortholary, Morgane Cheminant, Romain Guery, Claire Aguilar, Isabelle Schuffenecker, Marianne Leruez-Ville, Fanny Lanternier, Marc Lecuit, Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Imagine - Institut des maladies génétiques (IMAGINE - U1163), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), Centre National de Référence (CNR) des Enterovirus et Parechovirus [HCL Lyon], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Laboratoire de Microbiologie Clinique [AP-HP Hôpital Necker-Enfants Malades], CHU Necker - Enfants Malades [AP-HP], Service d'Hématologie Adulte, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], and Centre National de Référence (CNR) des Enterovirus et Parechovirus [HCL Lyon] (CNR - laboratoire associé)

Subjects
0301 basic medicine, Microbiology (medical), medicine.medical_specialty, viruses, [SDV]Life Sciences [q-bio], 030106 microbiology, education, 03 medical and health sciences, 0302 clinical medicine, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, 030212 general & internal medicine, health care economics and organizations, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, business.industry, virus diseases, Dermatology, Rash, 3. Good health, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, medicine.symptom, business, Palm, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; Diagnosis: Atypical hand, foot, and mouth disease caused by coxsackievirus A6 (CVA6).

Published
2017
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22. A new real-time RT-PCR targeting VP4-VP2 to detect and quantify enterovirus D68 in respiratory samples

Author

Johan Geiser, Isabelle Schuffenecker, Caroline Tapparel, Léna Royston, and Laurence Josset

Subjects
0301 basic medicine, 030106 microbiology, Biology, Real-Time Polymerase Chain Reaction, medicine.disease_cause, Sensitivity and Specificity, Genome, Disease Outbreaks, 03 medical and health sciences, Virology, Enterovirus Infections, medicine, Humans, Respiratory Tract Infections, Respiratory samples, Phylogeny, Enterovirus D, Human, Viral Structural Proteins, ddc:616, Outbreak, 3. Good health, Infectious Diseases, Real-time polymerase chain reaction, Enterovirus, Seasons, Enterovirus D68
Abstract

Causing an international outbreak of respiratory disease, Enterovirus D68 quickly entered the closed circle of emerging viral pathogens of public health significance. As rapid and accurate detection of EV-D68 is essential for an efficient clinical management, we designed and validated a new highly efficient one-step quantitative rRT-PCR specific to EV-D68 VP4-VP2 region. With 100% specificity and 95.6% sensitivity to all EV-D68 strains, this new assay can be reliably used to detect and quantify EV-D68 in respiratory samples and represents an interesting additional tool for diagnosis as it targets an original region of the genome.

Published
2017

23. Severe paediatric conditions linked with EV-A71 and EV-D68, France, May to October 2016

Author

Florence Moulin, Bruno Lina, Cécile Henquell, Audrey Mirand, Daniel Lévy-Bruhl, Isabelle Schuffenecker, Isabelle Desguerre, Marianne Leruez-Ville, Mélodie Aubart, Clément Bassi, Denise Antona, Manoelle Kossorotoff, CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hospices Civils de Lyon (HCL), Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Virologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), 'Personal Protection Against Vectors' working group (PPAV), PPAV working group, Unité des maladies à prévention vaccinale, Institut de Veille Sanitaire (INVS), CHU Clermont-Ferrand, Service de Neuropédiatrie, and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)

Subjects
Male, 0301 basic medicine, Pediatrics, Enterovirus Infections, Epidemiology, Enterovirus A71, medicine.disease_cause, Severity of Illness Index, Molecular typing, Medicine, Child, Respiratory Tract Infections, Phylogeny, ComputingMilieux_MISCELLANEOUS, Enterovirus D, Human, severe neurological symptoms, Respiratory tract infections, Coinfection, 3. Good health, Hospitalization, Child, Preschool, Female, France, Rapid Communication, medicine.medical_specialty, Adolescent, Genotype, 030106 microbiology, macromolecular substances, [SDV.MP.PRO]Life Sciences [q-bio]/Microbiology and Parasitology/Protistology, 03 medical and health sciences, children, Virology, Humans, Enterovirus D68, business.industry, Public Health, Environmental and Occupational Health, Infant, Sequence Analysis, DNA, Enterovirus a71, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, Enterovirus A, Human, Molecular Typing, 030104 developmental biology, Enterovirus, Nervous System Diseases, business, Sentinel Surveillance
Abstract

We report 59 cases of severe paediatric conditions linked with enterovirus (EV)-A71 and EV-D68 in France between May and October 2016. Fifty-two children had severe neurological symptoms. EV sequence-based typing for 42 cases revealed EV-A71 in 21 (18 subgenotype C1, detected for the first time in France) and EV-D68 in eight. Clinicians should be encouraged to obtain stool and respiratory specimens from patients presenting with severe neurological disorders for EV detection and characterisation.

Published
2016
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24. Disseminated rhinovirus C8 infection with infectious virus in blood and fatal outcome in a child with repeated episodes of bronchiolitis

Author

Bruno Lina, Patrice Morand, Nathalie Lin-Marq, Samuel Constant, Laurent Kaiser, Julie Bardet, Christine Morel-Baccard, Isabelle Schuffenecker, Johannes Alexander Lobrinus, Caroline Tapparel, Julien Lupo, Valérie Payen, Unit for Virus Host-Cell Interactions [Grenoble] (UVHCI), Centre National de la Recherche Scientifique (CNRS)-European Molecular Biology Laboratory [Grenoble] (EMBL)-Université Joseph Fourier - Grenoble 1 (UJF), French National Enterovirus/Parechovirus Reference centre, Hospices Civils de Lyon (HCL), Centre hospitalier universitaire de Grenoble (CHU de Grenoble), CHU Grenoble, and University of Geneva [Switzerland]

Subjects
Microbiology (medical), Virus Cultivation, Fatal outcome, Rhinovirus, Respiratory System, Viremia, Case Reports, medicine.disease_cause, Feces, 03 medical and health sciences, Fatal Outcome, 0302 clinical medicine, Cerebrospinal fluid, stomatognathic system, medicine, Humans, 030212 general & internal medicine, Respiratory system, Cerebrospinal Fluid, 030304 developmental biology, ddc:616, 0303 health sciences, Picornaviridae Infections, business.industry, Infant, virus diseases, medicine.disease, Virology, 3. Good health, [SDV.BBM.BS]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Biomolecules [q-bio.BM], Blood, Bronchiolitis, Immunology, Female, Airway, business
Abstract

We report a fatal case of acute lower respiratory tract disease with human rhinovirus C (HRV-C) as the unique cause in a 19-month-old girl with a history of repeated episodes of bronchiolitis. HRV-C type 8 nucleic acids were observed in respiratory, stool, and cerebrospinal fluid samples, and infectious virions were isolated from patient serum after inoculation onto reconstituted airway epithelia.

Published
2015

25. Transmission patterns of human enterovirus 71 to, from and among European countries, 2003 to 2013

Author

Agnes Farkas, Jean-Luc Bailly, Christine Archimbaud, Chervin Hassel, Hartwig P. Huemer, Isabelle Schuffenecker, Audrey Mirand, Alexander N. Lukashev, Cécile Henquell, Sabine Diedrich, Elena Terletskaia-Ladwig, Hélène Peigue-Lafeuille, Laboratoire Microorganismes : Génome et Environnement (LMGE), Université Clermont Auvergne [2017-2020] (UCA [2017-2020])-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Epidémiologie et pathogénie des infections à entérovirus (EPIE), and Université d'Auvergne - Clermont-Ferrand I (UdA)

Subjects
Genes, Viral, Genotype, Epidemiology, Molecular Sequence Data, Iceland, Zoology, Disease, Virus, Disease Outbreaks, 03 medical and health sciences, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Enterovirus 71, Enterovirus Infections, media_common.cataloged_instance, Humans, European Union, European union, Phylogeny, 030304 developmental biology, media_common, 0303 health sciences, Molecular Epidemiology, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Polymorphism, Genetic, Phylogenetic tree, biology, Molecular epidemiology, Geography, 030306 microbiology, Transmission (medicine), Norway, Public Health, Environmental and Occupational Health, Outbreak, Bayes Theorem, biology.organism_classification, 3. Good health, Enterovirus A, Human, Europe, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, RNA, Viral, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Sentinel Surveillance, Switzerland
Abstract

International audience; Enterovirus 71 (EV-71) is involved in epidemics of hand, foot, and mouth disease (HFMD) and has been reported to occur with severe neurological complications in eastern and southeast Asia. In other geographical areas, the transmission of this virus is poorly understood. We used large sequence datasets (of the gene encoding the viral protein 1, VP1) and a Bayesian phylogenetic approach to compare the molecular epidemiology and geographical spread patterns of EV-71 subgenogroups B4, B5, C1, C2, and C4 in Europe relative to other parts of the world. For the study, European countries considered were European Union (EU) Member States and Iceland, Norway and Switzerland. Viruses of the B4, B5, and C4 subgenogroups circulate mainly in eastern and southeast Asia. In Europe sporadic introductions of these subgenogroups are observed, however C1 and C2 viruses predominate. The phylogenies showed evidence of multiple events of spread involving C1 and C2 viruses within Europe since the mid-1990s. Two waves of sporadic C2 infections also occurred in 2010 and 2013. The 2007 Dutch outbreak caused by C2 and the occurrence of B5 and C4 infections in the EU between 2004 and 2013 arose while the circulation of C1 viruses was low. A transmission chain involving a C4 virus was traced from Japan to the EU and then further to Canada between 2001 and 2006. Recent events whereby spread of viruses have occurred from, to, and within Europe appear to be involved in the long term survival of EV-71, highlighting the need for enhanced surveillance of this virus.

Published
2015
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26. Fatal Case of Enterovirus 71 Infection and Rituximab Therapy, France, 2012

Author

Didier Gruson, Isabelle Schuffenecker, Somar Kassab, Tahar Saghi, Bruno Lina, Hervé Fleury, A. Boyer, Marie-Edith Lafon, Virology Laboratory, Bordeaux University Hospital, Bordeaux, France, CNRS-UMR 5234, Microbiologie fondamentale et Pathogénicité, University of Bordeaux 2, Bordeaux, France, Institut Français en Afrique du Sud ( IFAS ), Institut Français en Afrique du Sud, Langage, LAngues et Cultures d'Afrique Noire ( LLACAN ), Institut National des Langues et Civilisations Orientales ( Inalco ) -Université Paris Diderot - Paris 7 ( UPD7 ) -Centre National de la Recherche Scientifique ( CNRS ), Département d'Endocrinologie et Nutrition ( LOUVAIN - Endocrino ), Université Catholique de Louvain ( UCL ), Virologie et pathologie humaine ( VirPath ), Université Claude Bernard Lyon 1 ( UCBL ), Université de Lyon-Université de Lyon, Centre de Biologie et Pathologie Est, Bron, Microbiologie cellulaire et moléculaire et pathogénicité (MCMP), Université Bordeaux Segalen - Bordeaux 2-Centre National de la Recherche Scientifique (CNRS), Institut Français en Afrique du Sud (IFAS), Langage, LAngues et Cultures d'Afrique Noire (LLACAN), Institut National des Langues et Civilisations Orientales (Inalco)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Département d'Endocrinologie et Nutrition (LOUVAIN - Endocrino), Université Catholique de Louvain = Catholic University of Louvain (UCL), Virologie et pathologie humaine (VirPath), and Université Claude Bernard Lyon 1 (UCBL)

Subjects
Microbiology (medical), Pediatrics, medicine.medical_specialty, Letter, Epidemiology, Hospitalized patients, lcsh:Medicine, Asymptomatic, lcsh:Infectious and parasitic diseases, rituximab, Rituximab therapy, [ SDV.MP ] Life Sciences [q-bio]/Microbiology and Parasitology, Paralysis, medicine, Enterovirus 71, viruses, lcsh:RC109-216, Letters to the Editor, enterovirus 71, ComputingMilieux_MISCELLANEOUS, rhomboencephalitis, biology, business.industry, lcsh:R, Outbreak, biology.organism_classification, EV-71, Brainstem encephalitis, Infectious Diseases, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, Immunology, Rituximab, France, medicine.symptom, fatal case, business, medicine.drug
Abstract

To the Editor: Enterovirus 71 (EV-71) causes primarily asymptomatic or benign infections in children

Published
2013

27. Ex vivo and in vivo inhibition of human rhinovirus replication by a new pseudosubstrate of viral 2A protease

Author

Fatma Berri, Bruno Lina, Didier Decimo, Jean-Claude Cortay, Sébastien Violot, Isabelle Schuffenecker, Béatrice Riteau, Florence Morfin, Théophile Ohlmann, Marie-Laure Foucault-Grunenwald, Nisrine Falah, Virologie et pathologie humaine (VirPath), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Laboratoire de physiologie cellulaire végétale (LPCV), Université Joseph Fourier - Grenoble 1 (UJF)-Institut National de la Recherche Agronomique (INRA)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Virologie humaine, École normale supérieure - Lyon (ENS Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Biologie et Pathologie Est, Bron, Laboratory of Virology East, Hospices Civils de Lyon (HCL), Microbiologie moléculaire et biochimie structurale / Molecular Microbiology and Structural Biochemistry (MMSB), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), National Reference Center of Enteroviruses, Institut de Veille Sanitaire, Agence Nationale de la Recherche (ANR), Virologie et pathologie humaine ( VirPath ), Université Claude Bernard Lyon 1 ( UCBL ), Laboratoire de physiologie cellulaire végétale ( LPCV ), Université Joseph Fourier - Grenoble 1 ( UJF ) -Institut National de la Recherche Agronomique ( INRA ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ), École normale supérieure - Lyon ( ENS Lyon ) -IFR128-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Hospices Civils de Lyon ( HCL ), École normale supérieure de Lyon (ENS de Lyon)-IFR128-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre de Biologie et Pathologie Est [Bron] (CBPE)

Subjects
MESH : Molecular Sequence Data, Rhinovirus, AIRWAY INFLAMMATION, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Peptide, POLIOVIRUS, MESH: Amino Acid Sequence, medicine.disease_cause, Virus Replication, MESH: Down-Regulation, Substrate Specificity, MESH : Down-Regulation, Mice, MESH: Picornaviridae Infections, MESH : Female, MESH: Animals, MESH : Viral Proteins, Peptide sequence, chemistry.chemical_classification, MESH : Picornaviridae Infections, 0303 health sciences, Mice, Inbred BALB C, MESH: Rhinovirus, MESH : Substrate Specificity, MESH : Peptides, MESH: Peptides, MESH : Amino Acid Sequence, MESH : Sequence Alignment, 030302 biochemistry & molecular biology, MESH : Protein Binding, PEPTIDES, Cysteine protease, 3. Good health, MESH : Rhinovirus, MESH : Virus Replication, Cysteine Endopeptidases, INFECTIONS, MESH : Cysteine Endopeptidases, Female, Protein Binding, Immunology, Molecular Sequence Data, MESH: Mice, Inbred BALB C, MESH: Sequence Alignment, Down-Regulation, Biology, Microbiology, 03 medical and health sciences, Viral Proteins, In vivo, Virology, Vaccines and Antiviral Agents, MESH : Mice, medicine, Animals, Humans, MESH: Protein Binding, Amino Acid Sequence, MESH: Mice, MESH : Mice, Inbred BALB C, 030304 developmental biology, Protease, Picornaviridae Infections, MESH: Humans, MESH: Molecular Sequence Data, [ SDV ] Life Sciences [q-bio], STABILITY, CLEAVAGE, PROTEINASES, MESH : Humans, COXSACKIEVIRUS, MESH: Virus Replication, MESH: Viral Proteins, Viral replication, chemistry, Insect Science, RNA, MESH: Substrate Specificity, MESH : Animals, TRANSLATION, Sequence Alignment, MESH: Female, Ex vivo, MESH: Cysteine Endopeptidases
Abstract

Human rhinoviruses (HRVs) remain a significant public health problem as they are the major cause of both upper and lower respiratory tract infections. Unfortunately, to date no vaccine or antiviral against these pathogens is available. Here, using a high-throughput yeast two-hybrid screening, we identified a 6-amino-acid hit peptide, LVLQTM, which acted as a pseudosubstrate of the viral 2A cysteine protease (2A pro ) and inhibited its activity. This peptide was chemically modified with a reactive electrophilic fluoromethylketone group to form a covalent linkage with the nucleophilic active-site thiol of the enzyme. Ex vivo and in vivo experiments showed that thus converted, LVLQTM was a strong inhibitor of HRV replication in both A549 cells and mice. To our knowledge, this is the first report validating a compound against HRV infection in a mouse model.

Published
2012
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28. Prospective study of Chikungunya virus acute infection in the Island of La Réunion during the 2005-2006 outbreak

Author

Abdel Souab, Alain Michault, Karin Le Roux, Philippe Grivard, Frédérik Staikowsky, Marc Lecuit, François Talarmin, Isabelle Schuffenecker, CHU Sud Saint Pierre [Ile de la Réunion], Centre national de Référence et Centre Collaborateur de l'OMS Arbovirus (CNR-CCOMS), Institut Pasteur [Paris] (IP), Microorganismes et Barrières de l'Hôte (Equipe avenir), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service des Maladies infectieuses et tropicales [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris], and Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris]

Subjects
myalgia, Male, Critical Care and Emergency Medicine, [SDV]Life Sciences [q-bio], lcsh:Medicine, MESH: Comorbidity, Comorbidity, medicine.disease_cause, Dengue fever, Disease Outbreaks, 0302 clinical medicine, MESH: Aged, 80 and over, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Animals, 030212 general & internal medicine, Chikungunya, Prospective Studies, MESH: Disease Outbreaks, Prospective cohort study, MESH: Alphavirus Infections, lcsh:Science, Aged, 80 and over, MESH: Aged, Multidisciplinary, Leukopenia, MESH: Middle Aged, virus diseases, Middle Aged, Pharyngitis, 3. Good health, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Female, France, medicine.symptom, Chikungunya virus, Research Article, Infectious Diseases/Tropical and Travel-Associated Diseases, Adult, medicine.medical_specialty, Adolescent, 030231 tropical medicine, 03 medical and health sciences, Internal medicine, Infectious Diseases/Viral Infections, medicine, Animals, Humans, Alphavirus infection, Aged, MESH: Adolescent, MESH: Humans, business.industry, Alphavirus Infections, lcsh:R, Outbreak, MESH: Adult, MESH: Chikungunya virus, medicine.disease, MESH: Male, MESH: Prospective Studies, MESH: France, Culicidae, Infectious Diseases/Neglected Tropical Diseases, Immunology, lcsh:Q, business, MESH: Culicidae, MESH: Female, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

International audience; BackgroundChikungunya virus (CHIKV) is a recently re-emerged arthropod borne virus responsible for a massive outbreak in the Indian Ocean and India, and extended to Southeast Asia as well as Italy. CHIKV has adapted to Aedes albopictus, an anthropophilic mosquito species widely distributed in Asia, Europe, Africa and America. Our objective was to determine the clinical and biological features of patients at the acute phase of CHIKV infection.Methods and FindingsA prospective study enrolled 274 consecutive patients with febrile arthralgia recorded at the Emergency Department of the Groupe Hospitalier Sud-Réunion between March and May 2006. Three groups were defined: one group of 180 viremic patients (positive CHIKV RT-PCR), one group of 34 patients with acute post-viremic infection (negative CHIKV RT-PCR, positive anti-CHIKV IgM and negative IgG), and one group of 46 uninfected patients (negative CHIKV RT-PCR, anti-CHIKV IgM and IgG). Bivariate analyses of clinical and biological features between groups were performed. Patients with CHIKV viremia presented typically with asymmetrical bilateral polyarthralgia (96.5%) affecting the lower (98%) and small joints (74.8%), as well as asthenia (88.6%), headache (70%), digestive trouble (63.3%), myalgia (59%), exanthems (47.8%), conjunctival hyperhemia (23%) and adenopathy (8.9%). Vertigo, cutaneous dysesthesia, pharyngitis and haemorrhages were seldom observed. So far unreported symptoms such as chondrocostal arthralgia (20%), entesopathies (1.6%), talalgia (14%) were also noted. Prurit was less frequent during the viremic than post-viremic phase (13.9% vs. 41.2%; p

Published
2009
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29. Multidisciplinary Prospective Study of Mother-to-Child Chikungunya Virus Infections on the Island of La Réunion

Author

Yann Lenglet, Philippe Grivard, G. Barau, Ghassan Choker, Karin Le Roux, Fernando Arenzana-Seisdedos, Marc Lecuit, Patrick Gérardin, H Randrianaivo, Séverine Blanc, Alain Michault, Thérèse Couderc, Pierre-Yves Robillard, Marc Bintner, Yasmina Touret, Anne Bouveret, Isabelle Schuffenecker, Autard, Delphine, CIC régional épidémiologie clinique/essais cliniques - Ile de la Réunion (CIC-EC), Institut National de la Santé et de la Recherche Médicale (INSERM), Service de réanimation néonatologique et pédiatrique [La Réunion], Groupe Hospitalier Sud-CHR La réunion, Service de gynécologie-obstétrique [La réunion], Service de microbiologie, Service de neuroradiologie [La réunion], Service de médecine foetale et foetopathologie, Centre national de Référence et Centre Collaborateur de l'OMS Arbovirus (CNR-CCOMS), Institut Pasteur [Paris] (IP), Microorganismes et Barrières de l'Hôte (Equipe avenir), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Pathogénie Virale Moléculaire, Centre d'infectiologie Necker-Pasteur [CHU Necker], Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), This study was funded in part by the Institut Pasteur, the Agence Nationale pour la Recherche and INSERM. ML is a recipient of an INSERM interface contract, Centre d'Investigation Clinique Regional Epidemiologie Clinique/essais Cliniques - Ile de la Reunion, Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Pasteur [Paris], Equipe avenir Microorganismes et Barrières de l'Hôte, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), and Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP]

Subjects
Pediatrics, MESH : Prevalence, viruses, MESH: Brain Diseases, Pediatrics and Child Health, medicine.disease_cause, MESH: Magnetic Resonance Imaging, 0302 clinical medicine, MESH: Pregnancy, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Pregnancy, MESH: Reverse Transcriptase Polymerase Chain Reaction, Epidemiology, Pathology, Prevalence, MESH : Female, 030212 general & internal medicine, Chikungunya, Pregnancy Complications, Infectious, MESH : Infectious Disease Transmission, Vertical, Prospective cohort study, MESH: Alphavirus Infections, [SDV.MHEP.ME] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, 0303 health sciences, education.field_of_study, [SDV.MHEP.ME]Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Brain Diseases, [ SDV.MHEP.ME ] Life Sciences [q-bio]/Human health and pathology/Emerging diseases, Transmission (medicine), Reverse Transcriptase Polymerase Chain Reaction, MESH: Infant, Newborn, MESH : Reverse Transcriptase Polymerase Chain Reaction, virus diseases, General Medicine, Magnetic Resonance Imaging, MESH: Mothers, 3. Good health, MESH: Infectious Disease Transmission, Vertical, Obstetrics, [ SDV.MHEP.MI ] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Infectious Diseases, MESH : Mothers, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Medicine, Female, MESH: Reunion, Chikungunya virus, Research Article, medicine.medical_specialty, Mother to child transmission, Radiology and Medical Imaging, Population, Public Health and Epidemiology, Mothers, MESH : Brain Diseases, MESH : Chikungunya virus, MESH : Infant, Newborn, Virus, 03 medical and health sciences, MESH : Magnetic Resonance Imaging, Virology, medicine, Humans, MESH : Reunion, MESH: Pregnancy Complications, Infectious, education, MESH : Alphavirus Infections, MESH: Prevalence, 030304 developmental biology, MESH: Humans, business.industry, Alphavirus Infections, MESH : Humans, Infant, Newborn, Outbreak, Neonates, MESH: Chikungunya virus, Infectious Disease Transmission, Vertical, MESH : Pregnancy, MESH : Pregnancy Complications, Infectious, business, MESH: Female, Reunion
Abstract

Background An outbreak of chikungunya virus affected over one-third of the population of La Réunion Island between March 2005 and December 2006. In June 2005, we identified the first case of mother-to-child chikungunya virus transmission at the Groupe Hospitalier Sud-Réunion level-3 maternity department. The goal of this prospective study was to characterize the epidemiological, clinical, biological, and radiological features and outcomes of all the cases of vertically transmitted chikungunya infections recorded at our institution during this outbreak. Methods and Findings Over 22 mo, 7,504 women delivered 7,629 viable neonates; 678 (9.0%) of these parturient women were infected (positive RT-PCR or IgM serology) during antepartum, and 61 (0.8%) in pre- or intrapartum. With the exception of three early fetal deaths, vertical transmission was exclusively observed in near-term deliveries (median duration of gestation: 38 wk, range 35–40 wk) in the context of intrapartum viremia (19 cases of vertical transmission out of 39 women with intrapartum viremia, prevalence rate 0.25%, vertical transmission rate 48.7%). Cesarean section had no protective effect on transmission. All infected neonates were asymptomatic at birth, and median onset of neonatal disease was 4 d (range 3–7 d). Pain, prostration, and fever were present in 100% of cases and thrombocytopenia in 89%. Severe illness was observed in ten cases (52.6%) and mainly consisted of encephalopathy (n = 9; 90%). These nine children had pathologic MRI findings (brain swelling, n = 9; cerebral hemorrhages, n = 2), and four evolved towards persistent disabilities. Conclusions Mother-to-child chikungunya virus transmission is frequent in the context of intrapartum maternal viremia, and often leads to severe neonatal infection. Chikungunya represents a substantial risk for neonates born to viremic parturients that should be taken into account by clinicians and public health authorities in the event of a chikungunya outbreak., In a prospective study on the island of La Réunion, Marc Lecuit and colleagues find frequent transmission of Chikungunya virus by viremic mothers giving birth during an outbreak, resulting in serious infant illness., Editors' Summary Background. Chikungunya virus, an emerging infectious agent that is transmitted by day-biting mosquitoes, was first isolated from a patient in Tanzania in the early 1950s. Since then, major outbreaks of chikungunya fever have occurred throughout sub-Saharan Africa and in Southeast Asia, India, and the Western Pacific, usually at intervals of about 7–8 years. The virus causes fever, rash, severe joint and muscle pains, and sometimes arthritis (joint inflammation). These symptoms develop within 3–7 days of being bitten by an infected mosquito. Most people recover fully within a few weeks, but joint pain can sometimes continue for years. There is no treatment for chikungunya fever, but the symptoms can be eased with anti-inflammatory drugs. Preventative measures include covering arms and legs and using insecticides to avoid insect bites and depriving the mosquitoes of their breeding sites by draining standing water from man-made containers near human dwellings. Why Was This Study Done? In 2005, chikungunya fever appeared for the first time on several islands in the Indian Ocean. On La Réunion Island, the disease affected 300,000 people—more than one-third of the population—between March 2005 and December 2006. In June 2005, clinicians identified the first case of mother-to-child chikungunya virus transmission (vertical transmission). Public-health officials and clinicians need to know more about how often vertical transmission occurs and its clinical implications to help them prepare for future chikungunya fever outbreaks. In this study, the researchers identify and characterize all the cases of vertical chikungunya virus transmission that occurred at the largest hospital on La Réunion Island during the 2005–6 outbreak. What Did the Researchers Do and Find? The researchers enrolled all 7,504 women who gave birth at the hospital during the outbreak and their 7,629 children into their study. They then used “RT-PCR” (which detects the genome of virus particles during an active infection) and “IgM serology” (which looks for an immune response to recent infection) to determine which women had been infected with chikungunya virus during their pregnancy. 678 of the new mothers had been infected sometime between conception and a week before delivery, 22 mothers had been infected between 7 and 3 days before delivery, and 39 had been infected 2 days either side of delivery (the “intrapartum” period). Except for three early fetal deaths that were associated with chikungunya virus infections, vertical transmission was seen only in babies born to mothers infected with the virus intrapartum. 19 of the babies born to these women were infected with the virus—a vertical transmission rate of nearly 50%. The women who transmitted the virus to their offspring had more virus in their placenta than those who did not transmit the infection. Delivery by emergency cesarean section did not prevent transmission. All the infected babies were born healthy but developed fever, weakness, and pain within 3–7 days. In many of them, the number of platelets (clot-forming particles) in their blood also dropped dramatically. Ten babies became seriously ill—nine of them developed brain swelling; two had bleeding into their brain. Four children had lasting disabilities at the end of the study. What Do These Findings Mean? These findings show that mother-to-child transmission of chikungunya virus occurs frequently when women are infected with the virus at the time of delivery and that newborn children infected by this route can become very ill. Although these results do not find that cesarean section reduces infection rates, 90% of cesarean sections involving infected infants were performed urgently, rather than planned. The study also provides no information about whether delaying delivery, provided that no fetal distress is observed, until the mother's viral load has decreased might be beneficial. More studies are needed to provide a complete description of both the short-term and long-term effects of chikungunya virus infection in newborn babies, but it is clear that clinicians should monitor babies exposed to chikungunya virus during delivery for a week after their birth. Most importantly, clinicians and public-health officials will need to take account of the threat that the chikungunya virus poses to newborn children whenever and wherever it emerges. Additional Information. Please access these Web sites via the online version of this summary at http://dx.doi.org/10.1371/journal.pmed.0050060. Read the related PLoS Medicine Perspective article The World Health Organization provides information about chikungunya fever and a brief description of the recent chikungunya outbreak in the Indian Ocean (in English, French, Spanish, Arabic, Chinese, and Russian) The US Centers for Disease Control and Prevention has a fact sheet on chikungunya fever The UK Health Protection Agency also provides information about chikungunya virus, including news on recent outbreaks The French Institut de Veille Sanitaire (Institute for Public Health Surveillance) has a Web page on chikungunya (in French) The Institut Pasteur has a Web page on chikungunya research (in French and English)

Published
2008
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30. A Mouse Model for Chikungunya: Young Age and Inefficient Type-I Interferon Signaling Are Risk Factors for Severe Disease

Author

G. Barau, Fabrice Chrétien, Isabelle Schuffenecker, Olivier Disson, Thérèse Couderc, Alain Michault, Marc Lecuit, Matthew L. Albert, Florence Guivel-Benhassine, Nadège Cayet, Fernando Arenzana-Seisdedos, Clémentine Schilte, Philippe Desprès, Madly Brigitte, Yasmina Touret, Interactions Bactéries-Cellules (UIBC), Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Cellules Souches et Développement / Stem Cells and Development, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Groupe Henri Mondor-Albert Chenevier, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Immunobiologie des Cellules Dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Mondor de recherche biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Service de gynécologie-obstétrique [La réunion], Groupe Hospitalier Sud-CHR La réunion, Microscopie ultrastructurale (plate-forme), Institut Pasteur [Paris], Centre national de Référence et Centre Collaborateur de l'OMS Arbovirus (CNR-CCOMS), Interactions Moléculaires Flavivirus-Hôtes, Pathogénie Virale Moléculaire, Centre Hospitalier Universitaire de La Réunion (CHU La Réunion), Centre d'infectiologie Necker-Pasteur [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut Pasteur [Paris], This work received financial support from the Agence Nationale de la Recherche, Fondation pour la Recherche Médicale Inserm and Institut Pasteur (PTR 201). Marc Lecuit is the recipient of an Inserm interface contract., Vougny, Marie-Christine, Institut National de la Recherche Agronomique (INRA)-Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), Institut Pasteur [Paris] (IP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Institut Pasteur [Paris]-CHU Necker - Enfants Malades [AP-HP], Interactions Bactéries-Cellules ( UIBC ), Institut National de la Recherche Agronomique ( INRA ) -Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Cellules Souches et Développement, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique ( CNRS ), Assistance publique - Hôpitaux de Paris (AP-HP)-Hôpital Henri Mondor-Hôpital Albert Chenevier, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale ( INSERM ), Institut Mondor de recherche biomédicale ( IMRB ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Paris-Est Créteil Val-de-Marne - Paris 12 ( UPEC UP12 ), Centre Hospitalier Universitaire de La Réunion ( CHU La Réunion ), and Assistance publique - Hôpitaux de Paris (AP-HP)-CHU Necker - Enfants Malades [AP-HP]

Subjects
Male, Disease, Virus Replication, medicine.disease_cause, Mice, 0302 clinical medicine, Homo (Human), Chlorocebus aethiops, [ SDV.IMM ] Life Sciences [q-bio]/Immunology, Chikungunya, Biology (General), Mice, Knockout, 0303 health sciences, Age Factors, virus diseases, Mus (Mouse), Viral Load, 3. Good health, Infectious Diseases, Liver, Viruses, Interferon Type I, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Chikungunya virus, Viral load, Research Article, Signal Transduction, medicine.drug, Adult, [SDV.IMM] Life Sciences [q-bio]/Immunology, QH301-705.5, Longevity, 030231 tropical medicine, Immunology, Biology, Microbiology, Virus, 03 medical and health sciences, Cell Line, Tumor, Virology, Animals, Outbred Strains, Genetics, medicine, Animals, Humans, Alphavirus infection, Vero Cells, Molecular Biology, 030304 developmental biology, Alphavirus Infections, Infant, Newborn, RC581-607, medicine.disease, Mice, Inbred C57BL, Disease Models, Animal, Animals, Newborn, Viral replication, Tissue tropism, Parasitology, Immunologic diseases. Allergy, Interferon type I
Abstract

Chikungunya virus (CHIKV) is a re-emerging arbovirus responsible for a massive outbreak currently afflicting the Indian Ocean region and India. Infection from CHIKV typically induces a mild disease in humans, characterized by fever, myalgia, arthralgia, and rash. Cases of severe CHIKV infection involving the central nervous system (CNS) have recently been described in neonates as well as in adults with underlying conditions. The pathophysiology of CHIKV infection and the basis for disease severity are unknown. To address these critical issues, we have developed an animal model of CHIKV infection. We show here that whereas wild type (WT) adult mice are resistant to CHIKV infection, WT mouse neonates are susceptible and neonatal disease severity is age-dependent. Adult mice with a partially (IFN-α/βR+/−) or totally (IFN-α/βR−/−) abrogated type-I IFN pathway develop a mild or severe infection, respectively. In mice with a mild infection, after a burst of viral replication in the liver, CHIKV primarily targets muscle, joint, and skin fibroblasts, a cell and tissue tropism similar to that observed in biopsy samples of CHIKV-infected humans. In case of severe infections, CHIKV also disseminates to other tissues including the CNS, where it specifically targets the choroid plexuses and the leptomeninges. Together, these data indicate that CHIKV-associated symptoms match viral tissue and cell tropisms, and demonstrate that the fibroblast is a predominant target cell of CHIKV. These data also identify the neonatal phase and inefficient type-I IFN signaling as risk factors for severe CHIKV-associated disease. The development of a permissive small animal model will expedite the testing of future vaccines and therapeutic candidates., Author Summary Chikungunya virus (CHIKV) is transmitted by mosquito bites. CHIKV has recently re-emerged and is responsible for a massive outbreak in the Indian Ocean region and India. It has also reached Italy, indicating that CHIKV has a great potential to spread globally. Infection from CHIKV typically induces a mild disease in humans, characterized by a flu-like syndrome associated with muscle and joint pain and rash. Cases of severe infection involving the central nervous system (CNS) have recently been described, notably in neonates. We have developed the first animal model for CHIKV infection and studied the pathophysiology of the resulting disease. We show here that mouse neonates are susceptible to CHIKV and neonatal disease severity is age-dependent. Adult mice with a partial or complete defect in type-I interferon pathway develop a mild or severe infection, respectively. In mice with a mild infection, CHIKV primarily targets muscle, joint and skin fibroblasts, a cell and tissue tropism similar to that observed in biopsy samples of CHIKV-infected humans. In case of severe infections, CHIKV also disseminates to the CNS. Our work indicates that CHIKV-associated symptoms perfectly match viral tissue and cell tropisms, and demonstrate that the fibroblast is a prominent target cell of CHIKV. It also identifies the neonatal phase and inefficient type-I interferon signaling as risk factors for severe CHIKV-associated disease. The development of a permissive small animal model will expedite the testing of future vaccines and therapeutic candidates.

Published
2008
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31. Characterization of reemerging chikungunya virus

Author

Marie-Pascale Frenkiel, Philippe Desprès, Marion Sourisseau, Philippe V. Afonso, Fabien Blanchet, Fernando Arenzana-Seisdedos, Florence Guivel-Benhassine, Matthew L. Albert, Isabelle Schuffenecker, Ali Saïb, Pierre-Emmanuel Ceccaldi, Antoine Gessain, Olivier Schwartz, Nicoletta Casartelli, Dominika Rudnicka, Karin Le Roux, Céline Trouillet, Félix A. Rey, Simona Ozden, Clémentine Schilte, Alessia Zamborlini, Hafida Fsihi, Bruno Verhasselt, Alain Michault, Nathalie Sol-Foulon, Marie-Christine Prévost, Virus et Immunité, Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Immunobiologie des Cellules Dendritiques, Institut Pasteur [Paris]-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire de Microbiologie, Groupe Hospitalier Sud Réunion, Microscopie électronique (Plate-forme), Institut Pasteur [Paris], Département Infection et Epidémiologie - Department of Infection and Epidemiology, Interactions Moléculaires Flavivirus-Hôtes, Epidémiologie et Physiopathologie des Virus Oncogènes, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Universiteit Gent = Ghent University [Belgium] (UGENT), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Virologie Structurale, Pathogénie Virale Moléculaire, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP), Universiteit Gent = Ghent University (UGENT), Gau, Mireille, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)

Subjects
viruses, Virus Replication, medicine.disease_cause, Communicable Diseases, Emerging, Cytopathogenic Effect, Viral, Medicine and Health Sciences, MESH: Communicable Diseases, Emerging, MESH: Endothelial Cells, Chikungunya, Biology (General), MESH: Alphavirus Infections, [SDV.MP.VIR] Life Sciences [q-bio]/Microbiology and Parasitology/Virology, 0303 health sciences, biology, virus diseases, 3. Good health, Infectious Diseases, MESH: Epithelial Cells, Viruses, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, Polyarthritis, Antibody, Chikungunya virus, Encephalitis, Research Article, QH301-705.5, Immunology, Microbiology, Virus, 03 medical and health sciences, Indian Ocean Islands, Viral entry, Virology, Genetics, medicine, Humans, Molecular Biology, Tropism, MESH: Indian Ocean Islands, 030304 developmental biology, MESH: Humans, Alphavirus Infections, 030306 microbiology, MESH: Virus Replication, Endothelial Cells, Epithelial Cells, MESH: Chikungunya virus, RC581-607, medicine.disease, MESH: Cytopathogenic Effect, Viral, Viral replication, biology.protein, Parasitology, Immunologic diseases. Allergy
Abstract

An unprecedented epidemic of chikungunya virus (CHIKV) infection recently started in countries of the Indian Ocean area, causing an acute and painful syndrome with strong fever, asthenia, skin rash, polyarthritis, and lethal cases of encephalitis. The basis for chikungunya disease and the tropism of CHIKV remain unknown. Here, we describe the replication characteristics of recent clinical CHIKV strains. Human epithelial and endothelial cells, primary fibroblasts and, to a lesser extent, monocyte-derived macrophages, were susceptible to infection and allowed viral production. In contrast, CHIKV did not replicate in lymphoid and monocytoid cell lines, primary lymphocytes and monocytes, or monocyte-derived dendritic cells. CHIKV replication was cytopathic and associated with an induction of apoptosis in infected cells. Chloroquine, bafilomycin-A1, and short hairpin RNAs against dynamin-2 inhibited viral production, indicating that viral entry occurs through pH-dependent endocytosis. CHIKV was highly sensitive to the antiviral activity of type I and II interferons. These results provide a general insight into the interaction between CHIKV and its mammalian host., Author Summary Chikungunya virus (CHIKV) is a reemerging alphavirus responsible for an unprecedented epidemic in countries of the Indian Ocean region, causing an acute and painful syndrome with strong fever, asthenia, skin rash, polyarthritis, and lethal cases of encephalitis. The most recent epidemic reemergences were documented in Kinshasa, (50,000 estimated cases in 1999–2000), in Indonesia (2001–2003), the Indian Ocean islands of Mayotte, Mauritius, Réunion, and the Seychelles (270,000 cases in 2005–2006 in La Réunion island), and in India (1.4 to 6.5 million estimated cases in 2006–2007). There is a critical lack of knowledge on the biology of CHIKV. In particular, virtually nothing is known about the interaction of CHIKV (and of most alpahaviruses) with human primary cells. We have studied the replication characteristics and the tropism of clinical CHIKV strains from La Réunion. We designed various assays and reagents to follow viral replication, and we report here that adherent cells (epithelial and endothelial cells, primary fibroblasts), as well as macrophages, are sensitive to infection. In contrast, blood cells did not allow viral replication. We also characterized viral entry pathways and sensitivity to interferons. These results provide a general insight into the interaction between CHIKV and its mammalian host. This paper is the result of a collaborative effort between numerous teams from Institut Pasteur, the Groupe Hospitalier Sud Réunion, and other institutions. Our aim was to establish a task force with multiple and complementary expertise on virology, immunology, and cell biology in order to characterize this enigmatic virus.

Published
2007
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32. Retrospective survey of Chikungunya disease in Réunion Island hospital staff

Author

K. Le Roux, Alain Michault, A. Develay, Philippe Laurent, Philippe Grivard, Frédérik Staikowsky, Isabelle Schuffenecker, Service des Urgences [La Réunion], CHR La réunion-Groupe Hospitalier Sud Réunion (GHSR), Service de bactériologie, parasitologie, virologie et hygiène hospitalière [La réunion], Groupe Hospitalier Sud-CHR La réunion, Centre national de Référence et Centre Collaborateur de l'OMS Arbovirus (CNR-CCOMS), Institut Pasteur [Paris] (IP), and Institut Pasteur [Paris]

Subjects
Male, Pediatrics, Epidemiology, Anti-Inflammatory Agents, Disease, Disease Vectors, medicine.disease_cause, 0302 clinical medicine, Aedes, Surveys and Questionnaires, Chikungunya, 0303 health sciences, education.field_of_study, biology, Transmission (medicine), Age Factors, virus diseases, Middle Aged, Original Papers, Hospitals, 3. Good health, Infectious Diseases, Female, Viral disease, Chikungunya virus, Adult, medicine.medical_specialty, Aedes albopictus, Health Personnel, 030231 tropical medicine, Population, 03 medical and health sciences, Sex Factors, Retrospective survey, medicine, [CHIM]Chemical Sciences, Animals, Humans, education, 030304 developmental biology, Acetaminophen, Retrospective Studies, Plants, Medicinal, business.industry, Alphavirus Infections, biology.organism_classification, Surgery, business, Reunion
Abstract

SUMMARYRéunion Island (Indian Ocean) has been suffering from its first known Chikungunya virus (CHIKV) epidemic since February 2005. To achieve a better understanding of the disease, a questionnaire was drawn up for hospital staff members and their household. CHIKV infected about one-third of the studied population, the proportion increasing with age and being higher in women. Presence of a garden was associated with CHIKV infection. The geographical distribution of cases was concordant with insect vector Aedes albopictus distribution. The main clinical signs were arthralgia and fever. The disease evolved towards full recovery in 34·4% of cases, a relapse in 55·6%, or a chronic form in 10%. Paracetamol was used as a painkiller in 95% of cases, sometimes associated with non-steroidal anti-inflammatory drugs, corticoids, or traditional herbal medicine. The survey provided valuable information on the factors that favour transmission, the clinical signs, the importance of relapses and the therapies used.

Published
2007
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33. Two Chikungunya Isolates from the Outbreak of La Reunion (Indian Ocean) Exhibit Different Patterns of Infection in the Mosquito, Aedes albopictus

Author

Huot Khun, Anna-Bella Failloux, Isabelle Schuffenecker, Jean-Sébastien Dehecq, Marie Vazeille, Michel Huerre, Sara Moutailler, Philippe Desprès, D. Coudrier, Claudine Rousseaux, Didier Fontenille, Julien Thiria, Département de Virologie - Department of Virology, Institut Pasteur [Paris], Génétique Moléculaire des Bunyavirus, Cellule d'Intervention Biologique d'Urgence - Laboratory for Urgent Response to Biological Threats (CIBU), Histotechnologie et Pathologie, Direction Régionale des Affaires Sanitaires et Sociales de La Réunion, Caractérisation et contrôle des populations de vecteurs, Institut de Recherche pour le Développement (IRD), Biologie des Infections Virales Émergentes - Biology of Emerging Viral Infections (UBIVE), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Interactions Moléculaires Flavivirus-Hôtes, Cellule d'Intervention Biologique d'Urgence (CIBU), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris], Institut Pasteur [Paris] (IP), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur [Paris] (IP)

Subjects
Male, Aedes albopictus, Science, viruses, 030231 tropical medicine, Public Health and Epidemiology/Infectious Diseases, Aedes aegypti, medicine.disease_cause, Virus, Virology/Emerging Viral Diseases, Disease Outbreaks, 03 medical and health sciences, 0302 clinical medicine, Aedes, Infectious Diseases/Viral Infections, medicine, Animals, Chikungunya, Alphavirus infection, Phylogeny, 030304 developmental biology, 0303 health sciences, Multidisciplinary, biology, Alphavirus Infections, [SDV.BA]Life Sciences [q-bio]/Animal biology, Outbreak, virus diseases, [SDV.BBM.BM]Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, biology.organism_classification, medicine.disease, Virology, 3. Good health, Vector (epidemiology), Medicine, Female, Chikungunya virus, Research Article
Abstract

BackgroundA Chikungunya (CHIK) outbreak hit La Réunion Island in 2005-2006. The implicated vector was Aedes albopictus. Here, we present the first study on the susceptibility of Ae. albopictus populations to sympatric CHIKV isolates from La Réunion Island and compare it to other virus/vector combinations.Methodology and findingsWe orally infected 8 Ae. albopictus collections from La Réunion and 3 from Mayotte collected in March 2006 with two Chikungunya virus (CHIKV) from La Réunion: (i) strain 05.115 collected in June 2005 with an Alanine at the position 226 of the glycoprotein E1 and (ii) strain 06.21 collected in November 2005 with a substitution A226V. Two other CHIKV isolates and four additional mosquito strains/species were also tested. The viral titer of the infectious blood-meal was 10(7) plaque forming units (pfu)/mL. Dissemination rates were assessed by immunofluorescent staining on head squashes of surviving females 14 days after infection. Rates were at least two times higher with CHIKV 06.21 compared to CHIKV 05.115. In addition, 10 individuals were analyzed every day by quantitative RT-PCR. Viral RNA was quantified on (i) whole females and (ii) midguts and salivary glands of infected females. When comparing profiles, CHIKV 06.21 produced nearly 2 log more viral RNA copies than CHIKV 05.115. Furthermore, females infected with CHIKV 05.115 could be divided in two categories: weakly susceptible or strongly susceptible, comparable to those infected by CHIKV 06.21. Histological analysis detected the presence of CHIKV in salivary glands two days after infection. In addition, Ae. albopictus from La Réunion was as efficient vector as Ae. aegypti and Ae. albopictus from Vietnam when infected with the CHIKV 06.21.ConclusionsOur findings support the hypothesis that the CHIK outbreak in La Réunion Island was due to a highly competent vector Ae. albopictus which allowed an efficient replication and dissemination of CHIKV 06.21.

Published
2007
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34. Two-step strategy for the identification of SARS-CoV-2 variant of concern 202012/01 and other variants with spike deletion H69–V70, France, August to December 2020

Author

Bal, Antonin, Destras, Gregory, Gaymard, Alexandre, Stefic, Karl, Marlet, Julien, Eymieux, Sébastien, Regue, Hadrien, Semanas, Quentin, d’Aubarede, Constance, Billaud, Geneviève, Laurent, Frédéric, Gonzalez, Claudia, Mekki, Yahia, Valette, Martine, Bouscambert, Maude, Gaudy-Graffin, Catherine, Lina, Bruno, Morfin, Florence, Josset, Laurence, Casalegno, Jean-Sébastien, Frobert, Emilie, Escuret, Vanessa, Icard, Vinca, Jeannoel, Marion, Milon, Marie-Paule, Ramière, Christophe, Scholtès, Caroline, Tardy, Jean-Claude, Trabaud, Mary-Anne, Schuffenecker, Isabelle, Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR - laboratoire associé), Institut des Agents Infectieux [Lyon] (IAI), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hospices Civils de Lyon (HCL), Morphogénèse et antigénicité du VIH et du virus des Hépatites (MAVIVH - U1259 Inserm - CHRU Tours ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), The members of the COVID-Diagnosis HCL Study Group : Jean-Sébastien Casalegno, Emilie Frobert, Vanessa Escuret, Vinca Icard, Marion Jeannoel, Marie-Paule Milon, Christophe Ramière, Caroline Scholtès, Jean-Claude Tardy, Mary-Anne Trabaud, Isabelle Schuffenecker, Centre National de Référence des Virus des Infections Respiratoires (dont la Grippe) [Lyon] (CNR), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Marlet, Julien, Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Tours, and Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS)

Subjects
0301 basic medicine, 2019-20 coronavirus outbreak, Coronavirus disease 2019 (COVID-19), Epidemiology, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 030106 microbiology, Two step, spike protein, variants, deletion, Genome, Viral, Biology, spike protein, Genome, 03 medical and health sciences, COVID-19, whole genome sequencing, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Virology, Humans, Spike (database), Base sequence, Sequence Deletion, whole genome sequencing, variants, Base Sequence, deletion, SARS-CoV-2, Public Health, Environmental and Occupational Health, COVID-19, 030104 developmental biology, Spike Glycoprotein, Coronavirus, [SDV.MHEP.MI] Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Identification (biology), France, Rapid Communication
Abstract

International audience; We report the strategy leading to the first detection of variant of concern 202012/01 (VOC) in France (21 December 2020). First, the spike (S) deletion H69-V70 (ΔH69/ΔV70), identified in certain SARS-CoV-2 variants including VOC, is screened for. This deletion is associated with a S-gene target failure (SGTF) in the three-target RT-PCR assay (TaqPath kit). Subsequently, SGTF samples are whole genome sequenced. This approach revealed mutations co-occurring with ΔH69/ΔV70 including S:N501Y in the VOC.

Published
2021
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