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1. Evaluating stability of attenuated Sabin and two novel type 2 oral poliovirus vaccines in children

Author

Wahid, Rahnuma, Mercer, Laina, Gast, Chris, De Leon, Tirza, Sáez-Llorens, Xavier, Fix, Alan, Macadam, Andrew, Stephens, Laura, Chumakov, Konstantin, Smits, Saskia L, Murreddu, Marta, Konopka-Anstadt, Jennifer L, Steven Oberste, M, Burns, Cara C, Andino, Raul, Bachtiar, Novilia Sjafri, Tritama, Erman, Bandyopadhyay, Ananda S, Aguirre, Gabriela, Rüttimann, Ricardo, and Konz, John O

Subjects
Vaccine Related, Immunization, Prevention, Infectious Diseases, 2.1 Biological and endogenous factors, 3.4 Vaccines, Prevention of disease and conditions, and promotion of well-being, Aetiology, Infection, Good Health and Well Being
Abstract

Novel oral poliovirus vaccine type 2 (nOPV2) is being developed to reduce the rare occurrence of disease and outbreaks associated with the genetic instability of the Sabin vaccine strains. Children aged 1 to 5 years were enrolled in two related clinical studies to assess safety, immunogenicity, shedding rates and properties of the shed virus following vaccination with nOPV2 (two candidates) versus traditional Sabin OPV type 2 (mOPV2). The anticipated pattern of reversion and increased virulence was observed for shed Sabin-2 virus, as assessed using a mouse model of poliovirus neurovirulence. In contrast, there were significantly reduced odds of mouse paralysis for shed virus for both nOPV2 candidates when compared to shed Sabin-2 virus. Next-generation sequencing of shed viral genomes was consistent with and further supportive of the observed neurovirulence associated with shed Sabin-2 virus, as well as the reduced reversion to virulence of shed candidate viruses. While shed Sabin-2 showed anticipated A481G reversion in the primary attenuation site in domain V in the 5' untranslated region to be associated with increased mouse paralysis, the stabilized domain V in the candidate viruses did not show polymorphisms consistent with reversion to neurovirulence. The available data from a key target age group for outbreak response confirm the superior genetic and phenotypic stability of shed nOPV2 strains compared to shed Sabin-2 and suggest that nOPV2 should be associated with less paralytic disease and potentially a lower risk of seeding new outbreaks.

Published
2022

2. Evaluation and validation of next-generation sequencing to support lot release for a novel type 2 oral poliovirus vaccine

Author

Konz, John O, Schofield, Tim, Carlyle, Sarah, Wahid, Rahnuma, Ansari, Azeem, Strating, Jeroen RPM, Yeh, Ming Te, Manukyan, Hasmik, Smits, Saskia L, Tritama, Erman, Rahmah, Latri, Ugiyadi, Dori, Andino, Raul, Laassri, Majid, Chumakov, Konstantin, and Macadam, Andrew

Subjects
Immunization, Human Genome, Vaccine Related, Prevention, Genetics, Biotechnology, Infection, Good Health and Well Being, Next-generation sequencing, Validation, Poliovirus, OPV, Neurovirulence, G: IU, genome to infectious unit ratio, GCV, Geometric coefficient of variation, NGS, next-generation sequencing, OPV, oral poliovirus vaccine, SNP, single-nucleotide polymorphism, TNP, tri-nucleotide polymorphism, cVDPV, circulating vaccine-derived poliovirus, nOPV2, type 2 novel oral poliovirus vaccine
Abstract

A novel, genetically-stabilized type 2 oral polio vaccine (nOPV2), developed to assist in the global polio eradication program, was recently the first-ever vaccine granted Emergency Use Listing by the WHO. Lot release tests for this vaccine included-for the first time to our knowledge-the assessment of genetic heterogeneity using next-generation sequencing (NGS). NGS ensures that the genetically-modified regions of the vaccine virus genome remain as designed and that levels of polymorphisms which may impact safety or efficacy are controlled during routine production. The variants present in nOPV2 lots were first assessed for temperature sensitivity and neurovirulence using molecular clones to inform which polymorphisms warranted formal evaluation during lot release. The novel use of NGS as a lot release test required formal validation of the method. Analysis of an nOPV2 lot spiked with the parental Sabin-2 strain enabled performance characteristics of the method to be assessed simultaneously at over 40 positions in the genome. These characteristics included repeatability and intermediate precision of polymorphism measurement, linearity of both spike-induced and nOPV2 lot-specific polymorphisms, and the limit-of-detection of spike-induced polymorphisms. The performance characteristics of the method met pre-defined criteria for 34 spike-induced polymorphic sites and 8 polymorphisms associated with the nOPV2 preparation; these sites collectively spanned most of the viral genome. Finally, the co-location of variants of interest on genomes was evaluated, with implications for the interpretation of NGS discussed.

Published
2021

4. Virus genomes reveal factors that spread and sustained the Ebola epidemic

Author

Dudas, Gytis, Carvalho, Luiz Max, Bedford, Trevor, Tatem, Andrew J, Baele, Guy, Faria, Nuno R, Park, Daniel J, Ladner, Jason T, Arias, Armando, Asogun, Danny, Bielejec, Filip, Caddy, Sarah L, Cotten, Matthew, D’Ambrozio, Jonathan, Dellicour, Simon, Di Caro, Antonino, Diclaro, Joseph W, Duraffour, Sophie, Elmore, Michael J, Fakoli, Lawrence S, Faye, Ousmane, Gilbert, Merle L, Gevao, Sahr M, Gire, Stephen, Gladden-Young, Adrianne, Gnirke, Andreas, Goba, Augustine, Grant, Donald S, Haagmans, Bart L, Hiscox, Julian A, Jah, Umaru, Kugelman, Jeffrey R, Liu, Di, Lu, Jia, Malboeuf, Christine M, Mate, Suzanne, Matthews, David A, Matranga, Christian B, Meredith, Luke W, Qu, James, Quick, Joshua, Pas, Suzan D, Phan, My VT, Pollakis, Georgios, Reusken, Chantal B, Sanchez-Lockhart, Mariano, Schaffner, Stephen F, Schieffelin, John S, Sealfon, Rachel S, Simon-Loriere, Etienne, Smits, Saskia L, Stoecker, Kilian, Thorne, Lucy, Tobin, Ekaete Alice, Vandi, Mohamed A, Watson, Simon J, West, Kendra, Whitmer, Shannon, Wiley, Michael R, Winnicki, Sarah M, Wohl, Shirlee, Wölfel, Roman, Yozwiak, Nathan L, Andersen, Kristian G, Blyden, Sylvia O, Bolay, Fatorma, Carroll, Miles W, Dahn, Bernice, Diallo, Boubacar, Formenty, Pierre, Fraser, Christophe, Gao, George F, Garry, Robert F, Goodfellow, Ian, Günther, Stephan, Happi, Christian T, Holmes, Edward C, Kargbo, Brima, Keïta, Sakoba, Kellam, Paul, Koopmans, Marion PG, Kuhn, Jens H, Loman, Nicholas J, Magassouba, N’Faly, Naidoo, Dhamari, Nichol, Stuart T, Nyenswah, Tolbert, Palacios, Gustavo, Pybus, Oliver G, Sabeti, Pardis C, Sall, Amadou, Ströher, Ute, Wurie, Isatta, Suchard, Marc A, Lemey, Philippe, and Rambaut, Andrew

Subjects
Infectious Diseases, Emerging Infectious Diseases, Biodefense, Vaccine Related, Prevention, Infection, Good Health and Well Being, Climate, Disease Outbreaks, Ebolavirus, Genome, Viral, Geography, Hemorrhagic Fever, Ebola, Humans, Internationality, Linear Models, Molecular Epidemiology, Phylogeny, Travel, General Science & Technology
Abstract

The 2013-2016 West African epidemic caused by the Ebola virus was of unprecedented magnitude, duration and impact. Here we reconstruct the dispersal, proliferation and decline of Ebola virus throughout the region by analysing 1,610 Ebola virus genomes, which represent over 5% of the known cases. We test the association of geography, climate and demography with viral movement among administrative regions, inferring a classic 'gravity' model, with intense dispersal between larger and closer populations. Despite attenuation of international dispersal after border closures, cross-border transmission had already sown the seeds for an international epidemic, rendering these measures ineffective at curbing the epidemic. We address why the epidemic did not spread into neighbouring countries, showing that these countries were susceptible to substantial outbreaks but at lower risk of introductions. Finally, we reveal that this large epidemic was a heterogeneous and spatially dissociated collection of transmission clusters of varying size, duration and connectivity. These insights will help to inform interventions in future epidemics.

Published
2017

5. Assessment of genetic changes and neurovirulence of shed Sabin and novel type 2 oral polio vaccine viruses

Author

Wahid, Rahnuma, Mercer, Laina, Macadam, Andrew, Carlyle, Sarah, Stephens, Laura, Martin, Javier, Chumakov, Konstantin, Laassri, Majid, Petrovskaya, Svetlana, Smits, Saskia L., Stittelaar, Koert J., Gast, Chris, Weldon, William C., Konopka-Anstadt, Jennifer L., Steven Oberste, M., Van Damme, Pierre, De Coster, Ilse, Rüttimann, Ricardo, Bandyopadhyay, Ananda, and Konz, John

Published
2021
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8. Global Microbial Identifier

Author

Wielinga, Peter R., Hendriksen, Rene S., Aarestrup, Frank M., Lund, Ole, Smits, Saskia L., Koopmans, Marion P. G., Schlundt, Jørgen, Doyle, Michael P., Series editor, Deng, Xiangyu, editor, den Bakker, Henk C., editor, and Hendriksen, Rene S., editor

Published
2017
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11. Detection of circovirus in foxes with meningoencephalitis, United Kingdom, 2009-2013

Author

Bexton, Steve, Wiersma, Lidewij C., Getu, Sarah, van Run, Peter R., Verjans, Georges M.G.M., Schipper, Debby, Schapendonk, Claudia M.E., Bodewes, Rogier, Oldroyd, Lucy, Haagmans, Bart L., Koopmans, Marion M.P., and Smits, Saskia L.

Subjects
Meningococcal infections -- Physiological aspects, Animal diseases -- Diagnosis, DNA virus infections -- Diagnosis, Health
Abstract

Circoviruses (family Circoviridae) are nonenveloped, single-stranded, circular DNA ([approximately equal to] 2 kb) viruses (1). Two genera, Circovirus and Gyrovirus, are recognized, and an additional genus, Cyclovirus, has been proposed [...]

Published
2015
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16. Novel divergent rhabdovirus in feces of red fox, Spain

Author

Bodewes, Rogier, Ruiz-Gonzalez, Aritz, Schurch, Anita C., Osterhaus, Albert D.M.E., and Smits, Saskia L.

Subjects
Animals -- Diseases, Host-parasite relationships -- Genetic aspects, Health
Abstract

To the Editor: Rhabdoviruses (family Rhabdoviridae) are enveloped single-stranded negative-sense RNA viruses belonging to the Mononega-virales order. The International Committee on Taxonomy of Viruses recognizes 11 genera (Cytorhabdovirus, Ephemerovirus, Lyssavirus, [...]

Published
2014

17. Comparison of sequencing methods and data processing pipelines for whole genome sequencing and minority single nucleotide variant (mSNV) analysis during an influenza A/H5N8 outbreak

Author

Poen, Marjolein, Pohlmann, A, Amid, C, Bestebroer, Theo, Brookes, S M, Brown, IH, Everett, H, Schapendonk, Claudia, Scheuer, Rachel, Smits, Saskia, Beer, M, Fouchier, Ron, Ellis, RJ, Poen, Marjolein, Pohlmann, A, Amid, C, Bestebroer, Theo, Brookes, S M, Brown, IH, Everett, H, Schapendonk, Claudia, Scheuer, Rachel, Smits, Saskia, Beer, M, Fouchier, Ron, and Ellis, RJ

Published
2020

18. Comparison of sequencing methods and data processing pipelines for whole genome sequencing and minority single nucleotide variant (mSNV) analysis during an influenza A/H5N8 outbreak

Author

Poen, Marjolein J., primary, Pohlmann, Anne, additional, Amid, Clara, additional, Bestebroer, Theo M., additional, Brookes, Sharon M., additional, Brown, Ian H., additional, Everett, Helen, additional, Schapendonk, Claudia M. E., additional, Scheuer, Rachel D., additional, Smits, Saskia L., additional, Beer, Martin, additional, Fouchier, Ron A. M., additional, and Ellis, Richard J., additional

Published
2020
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19. Nontraumatic Myelopathy in Malawi: A Prospective Study in an Area with High HIV Prevalence

Author

Zijlstra, Eduard E., primary, van Hellemond, Jaap J., additional, Moes, Arthur D., additional, de Boer, Christa, additional, Boeschoten, Shelley A., additional, van Blijswijk, Catharina E. M., additional, van der Vuurst de Vries, Roos M., additional, Bailey, Peter A. B., additional, Kampondeni, Sam, additional, van Lieshout, Lisette, additional, Smits, Saskia L., additional, Katchanov, Juri, additional, Mkandawire, Nyengo M., additional, and Rothe, Camilla, additional

Published
2020
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20. Machine-learning based patient classification using Hepatitis B virus full-length genome quasispecies from Asian and European cohorts

Author

Mueller-Breckenridge, Alan J., primary, Garcia-Alcalde, Fernando, additional, Wildum, Steffen, additional, Smits, Saskia L., additional, de Man, Robert A., additional, van Campenhout, Margo J. H., additional, Brouwer, Willem P., additional, Niu, Jianjun, additional, Young, John A. T., additional, Najera, Isabel, additional, Zhu, Lina, additional, Wu, Daitze, additional, Racek, Tomas, additional, Hundie, Gadissa Bedada, additional, Lin, Yong, additional, Boucher, Charles A., additional, van de Vijver, David, additional, and Haagmans, Bart L., additional

Published
2019
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21. Machine-learning based patient classification using Hepatitis B virus full-length genome quasispecies from Asian and European cohorts

Author

Mueller-Breckenridge, AJ, Garcia-Alcalde, F, Wildum, S, Smits, Saskia, de Man, Rob, van Campenhout, Margo, Brouwer, Willem Pieter, Niu, JJ, Young, JAT, Najera, I, Zhu, LN, Wu, D, Racek, T, Hundie, Gadissa, Lin, Y, Boucher, Charles, van de Vijver, David, Haagmans, Bart, Mueller-Breckenridge, AJ, Garcia-Alcalde, F, Wildum, S, Smits, Saskia, de Man, Rob, van Campenhout, Margo, Brouwer, Willem Pieter, Niu, JJ, Young, JAT, Najera, I, Zhu, LN, Wu, D, Racek, T, Hundie, Gadissa, Lin, Y, Boucher, Charles, van de Vijver, David, and Haagmans, Bart

Published
2019

22. Spatiotemporal Analysis of the Genetic Diversity of Seal Influenza A(H10N7) Virus, Northwestern Europe

Author

Bodewes, Rogier, Zohari, Siamak, Krog, Jesper S, Hall, Matthew D, Harder, Timm C, Bestebroer, Theo M, van de Bildt, Marco W G, Spronken, Monique I, Larsen, Lars E, Siebert, Ursula, Wohlsein, Peter, Puff, Christina, Seehusen, Frauke, Baumgärtner, Wolfgang, Härkönen, Tero, Smits, Saskia L, Herfst, Sander, Osterhaus, Albert D M E, Fouchier, Ron A M, Koopmans, Marion P, Kuiken, Thijs, LS GZ Landbouwhuisdieren, Bedrijfsvoering, dFAH I&I, Virology, Schultz-Cherry, S., LS GZ Landbouwhuisdieren, Bedrijfsvoering, and dFAH I&I

Subjects
0301 basic medicine, viruses, Immunology, Hemagglutinin (influenza), Hemagglutinin Glycoproteins, Influenza Virus, Genome, Viral, Phoca, Biology, medicine.disease_cause, Microbiology, H5N1 genetic structure, Virus, 03 medical and health sciences, Spatio-Temporal Analysis, Orthomyxoviridae Infections, Virology, Influenza A virus, medicine, Animals, 14. Life underwater, Influenza A Virus, H10N7 Subtype, Phylogeny, Host (biology), Computational Biology, Genetic Variation, High-Throughput Nucleotide Sequencing, Outbreak, Influenza A virus subtype H5N1, 3. Good health, Europe, Phylogeography, 030104 developmental biology, Amino Acid Substitution, Genetic Diversity and Evolution, Insect Science, biology.protein, Neuraminidase
Abstract

Influenza A viruses are major pathogens for humans, domestic animals, and wildlife, and these viruses occasionally cross the species barrier. In spring 2014, increased mortality of harbor seals ( Phoca vitulina ), associated with infection with an influenza A(H10N7) virus, was reported in Sweden and Denmark. Within a few months, this virus spread to seals of the coastal waters of Germany and the Netherlands, causing the death of thousands of animals. Genetic analysis of the hemagglutinin (HA) and neuraminidase (NA) genes of this seal influenza A(H10N7) virus revealed that it was most closely related to various avian influenza A(H10N7) viruses. The collection of samples from infected seals during the course of the outbreak provided a unique opportunity to follow the adaptation of the avian virus to its new seal host. Sequence data for samples collected from 41 different seals from four different countries between April 2014 and January 2015 were obtained by Sanger sequencing and next-generation sequencing to describe the molecular epidemiology of the seal influenza A(H10N7) virus. The majority of sequence variation occurred in the HA gene, and some mutations corresponded to amino acid changes not found in H10 viruses isolated from Eurasian birds. Also, sequence variation in the HA gene was greater at the beginning than at the end of the epidemic, when a number of the mutations observed earlier had been fixed. These results imply that when an avian influenza virus jumps the species barrier from birds to seals, amino acid changes in HA may occur rapidly and are important for virus adaptation to its new mammalian host. IMPORTANCE Influenza A viruses are major pathogens for humans, domestic animals, and wildlife. In addition to the continuous circulation of influenza A viruses among various host species, cross-species transmission of influenza A viruses occurs occasionally. Wild waterfowl and shorebirds are the main reservoir for most influenza A virus subtypes, and spillover of influenza A viruses from birds to humans or other mammalian species may result in major outbreaks. In the present study, various sequencing methods were used to elucidate the genetic changes that occurred after the introduction and subsequent spread of an avian influenza A(H10N7) virus among harbor seals of northwestern Europe by use of various samples collected during the outbreak. Such detailed knowledge of genetic changes necessary for introduction and adaptation of avian influenza A viruses to mammalian hosts is important for a rapid risk assessment of such viruses soon after they cross the species barrier.

Published
2016

23. Influenza A/H3N2 virus infection in immunocompromised ferrets and emergence of antiviral resistance

Author

Roosenhoff, Rueshandra, van der Vries, Erhard, van der Linden, Anne, van Amerongen, Geert, Stittelaar, Koert J, Smits, Saskia L, Schutten, Martin, Fouchier, Ron A M, LS Virologie, dIRAS RA-1, dI&I I&I-1, Sub Physics Education, LS Virologie, dIRAS RA-1, dI&I I&I-1, Sub Physics Education, Virology, and Public Health

Subjects
0301 basic medicine, RNA viruses, Influenza Viruses, Viral Diseases, viruses, lcsh:Medicine, Drug resistance, medicine.disease_cause, Pathology and Laboratory Medicine, chemistry.chemical_compound, 0302 clinical medicine, Influenza A virus, Medicine and Health Sciences, 030212 general & internal medicine, lcsh:Science, Mammals, Multidisciplinary, biology, Reverse Transcriptase Polymerase Chain Reaction, Microbial Mutation, Eukaryota, virus diseases, Resistance mutation, 3. Good health, Infectious Diseases, Medical Microbiology, Viral Pathogens, Vertebrates, Viruses, Pathogens, Anatomy, Research Article, Oseltamivir, Substitution Mutation, Nose, Microbiology, Antiviral Agents, Virus, Throat, 03 medical and health sciences, Immunocompromised Host, Orthomyxoviridae Infections, Microbial Control, Drug Resistance, Viral, medicine, Genetics, Animals, Viral shedding, Microbial Pathogens, Pharmacology, business.industry, Influenza A Virus, H3N2 Subtype, lcsh:R, Organisms, Ferrets, Biology and Life Sciences, Virology, Influenza, 030104 developmental biology, Viral replication, chemistry, Face, Amniotes, Mutation, biology.protein, lcsh:Q, Antimicrobial Resistance, business, Neuraminidase, Head, Neck, Orthomyxoviruses
Abstract

Influenza viruses can cause severe life threatening infections in high-risk patients, including young children, the elderly and patients with compromised immunity due to underlying medical conditions or immunosuppressive treatment. The impaired immunity of these patients causes prolonged virus infection and combined with antiviral treatment facilitates the emergence of viruses with resistance mutations. The diverse nature of their immune status makes them a challenging group to study the impact of influenza virus infection and the efficacy of antiviral therapy. Immunocompromised ferrets may represent a suitable animal model to assess influenza virus infection and antiviral treatment strategies in immunocompromised hosts. Here, ferrets were given a daily oral solution of mycophenolate mofetil, tacrolimus and prednisolone sodium phosphate to suppress their immune system. Groups of immunocompromised and immunocompetent ferrets were inoculated with an A/H3N2 influenza virus and were subsequently treated with Oseltamivir or left untreated. Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) was performed on the throat and nose specimens to study virus replication during the course of infection. All immunocompromised ferrets had prolonged presence of viral RNA and a higher total amount of virus shedding compared to the immunocompetent ferrets. Although Oseltamivir reduced the total amount of virus shedding from the nose and throat of treated ferrets, it also resulted in the emergence of the neuraminidase R292K resistance substitution in all these animals, as determined by mutation specific RT-PCR and next-generation sequencing. No additional mutations that could be associated with the emergence of the R292K resistance mutation were detected. The immunocompromised ferret model can be used to study A/H3N2 virus shedding and is a promising model to study new antiviral strategies and the emergence of antiviral resistance in immunocompromised hosts.

Published
2018

24. Safety and efficacy of monoclonal antibody VIS410 in adults with uncomplicated influenza A infection: Results from a randomized, double-blind, phase-2, placebo-controlled study

Author

Hershberger, Ellie, primary, Sloan, Susan, additional, Narayan, Kristin, additional, Hay, Catherine A., additional, Smith, Patrick, additional, Engler, Frank, additional, Jeeninga, Rienk, additional, Smits, Saskia, additional, Trevejo, Jose, additional, Shriver, Zach, additional, and Oldach, David, additional

Published
2019
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26. Influenza A/H3N2 virus infection in immunocompromised ferrets and emergence of antiviral resistance

Author

LS Virologie, dIRAS RA-1, dI&I I&I-1, Sub Physics Education, Roosenhoff, Rueshandra, van der Vries, Erhard, van der Linden, Anne, van Amerongen, Geert, Stittelaar, Koert J, Smits, Saskia L, Schutten, Martin, Fouchier, Ron A M, LS Virologie, dIRAS RA-1, dI&I I&I-1, Sub Physics Education, Roosenhoff, Rueshandra, van der Vries, Erhard, van der Linden, Anne, van Amerongen, Geert, Stittelaar, Koert J, Smits, Saskia L, Schutten, Martin, and Fouchier, Ron A M

Published
2018

27. Virus discovery analyses on post-mortem brain tissue and cerebrospinal fluid of schizophrenia patients

Author

MMB Staf diagnostiek, UMC Utrecht, Onderzoeksgroep 11, Brain, Onderzoeksgroep 5, Tomasik, Jakub, Smits, Saskia L., Leweke, F. Markus, Eljasz, Paweł, Pas, Suzan, Kahn, René S., Osterhaus, Albert D.M.E., Bahn, Sabine, de Witte, Lot D., MMB Staf diagnostiek, UMC Utrecht, Onderzoeksgroep 11, Brain, Onderzoeksgroep 5, Tomasik, Jakub, Smits, Saskia L., Leweke, F. Markus, Eljasz, Paweł, Pas, Suzan, Kahn, René S., Osterhaus, Albert D.M.E., Bahn, Sabine, and de Witte, Lot D.

Published
2018

30. Safety and Efficacy of Monoclonal Antibody VIS410 in Adults with Uncomplicated Influenza A Infection: Results from a Randomised, Double-Blind, Placebo-Controlled Study

Author

Hershberger, Ellie, primary, Sloan, Susan, additional, Narayan, Kristin, additional, Hay, Catherine A., additional, Smith, Patrick, additional, Engler, Frank, additional, Jeeninga, Rienk, additional, Smits, Saskia, additional, Trevejo, Jose, additional, Shriver, Zach, additional, and Oldach, David, additional

Published
2018
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31. Identification of HCV Resistant Variants against Direct Acting Antivirals in Plasma and Liver of Treatment Naive Patients

Author

Victor, Stalinraj, Hundie, Gadissa, Schürch, Anita, Smits, Saskia, Pas, Suzan, Le Pogam, S, Janssen, HLA, de Knegt, Rob, Osterhaus, A, Najera, I, Boucher, Charles, Haagmans, Bart, Victor, Stalinraj, Hundie, Gadissa, Schürch, Anita, Smits, Saskia, Pas, Suzan, Le Pogam, S, Janssen, HLA, de Knegt, Rob, Osterhaus, A, Najera, I, Boucher, Charles, and Haagmans, Bart

Published
2017

32. The sample of choice for detecting Middle East respiratory syndrome coronavirus in asymptomatic dromedary camels using real-time reverse-transcription polymerase chain reaction

Author

Mohran, KA, Farag, EABA, Reusken, Chantal, Victor, Stalinraj, Lamers, Mart, Pas, Suzan, Kreeft - Voermans, Jolanda, Smits, Saskia, AlHajri, MM, Alhajri, F, Al-Romaihi, HE, Ghobashy, H, El-Maghraby, MM, Al Dhahiry, SHS, Al-Mawlawi, N, El-Sayed, AM, Al-Thani, M, Al-Marri, SA, Haagmans, Bart, Koopmans, Marion, and Virology

Published
2016

33. Identification of HCV Resistant Variants against Direct Acting Antivirals in Plasma and Liver of Treatment Naïve Patients

Author

Raj, V. Stalin, primary, Hundie, Gadissa Bedada, additional, Schürch, Anita C., additional, Smits, Saskia L., additional, Pas, Suzan D., additional, Le Pogam, Sophie, additional, Janssen, Harry L. A., additional, de Knegt, Rob J., additional, Osterhaus, Albert D. M. E., additional, Najera, Isabel, additional, Boucher, Charles A., additional, and Haagmans, Bart L., additional

Published
2017
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37. Identification of protein receptors for coronaviruses by mass spectrometry

Author

Raj, V Stalin, Lamers, Mart M, Smits, Saskia L, Demmers, Jeroen A A, Mou, Huihui, Bosch, Berend-Jan, Haagmans, Bart L, Maier, Helena Jane, Bickerton, Erica, Britton, Paul, LS Virologie, and dI&I I&I-1

Subjects
Mass spectrometry, Coronacrisis-Taverne, Immunoprecipitation, DPP4, Middle East respiratory syndrome coronavirus, Receptor
Abstract

As obligate intracellular parasites, viruses need to cross the plasma membrane and deliver their genome inside the cell. This step is initiated by the recognition of receptors present on the host cell surface. Receptors can be major determinants of tropism, host range, and pathogenesis. Identifying virus receptors can give clues to these aspects and can lead to the design of intervention strategies. Interfering with receptor recognition is an attractive antiviral therapy, since it occurs before the viral genome has reached the relative safe haven within the cell. This chapter describes the use of an immunoprecipitation approach with Fc-tagged viral spike proteins followed by mass spectrometry to identify and characterize the receptor for the Middle East respiratory syndrome coronavirus. This technique can be adapted to identify other viral receptors.

Published
2015

38. Spatiotemporal analysis of the genetic diversity of seal influenza A(H10N7) virus, Northwestern Europe

Author

LS GZ Landbouwhuisdieren, Bedrijfsvoering, dFAH I&I, Bodewes, Rogier, Zohari, Siamak, Krog, Jesper S, Hall, Matthew D, Harder, Timm C, Bestebroer, Theo M, van de Bildt, Marco W G, Spronken, Monique I, Larsen, Lars E, Siebert, Ursula, Wohlsein, Peter, Puff, Christina, Seehusen, Frauke, Baumgärtner, Wolfgang, Härkönen, Tero, Smits, Saskia L, Herfst, Sander, Osterhaus, Albert D M E, Fouchier, Ron A M, Koopmans, Marion P, Kuiken, Thijs, LS GZ Landbouwhuisdieren, Bedrijfsvoering, dFAH I&I, Bodewes, Rogier, Zohari, Siamak, Krog, Jesper S, Hall, Matthew D, Harder, Timm C, Bestebroer, Theo M, van de Bildt, Marco W G, Spronken, Monique I, Larsen, Lars E, Siebert, Ursula, Wohlsein, Peter, Puff, Christina, Seehusen, Frauke, Baumgärtner, Wolfgang, Härkönen, Tero, Smits, Saskia L, Herfst, Sander, Osterhaus, Albert D M E, Fouchier, Ron A M, Koopmans, Marion P, and Kuiken, Thijs

Published
2016

39. An orthopoxvirus-based vaccine reduces virus excretion after MERS-CoV infection in dromedary camels

Author

Haagmans, Bart L, van den Brand, Judith M A, Raj, V Stalin, Volz, Asisa, Wohlsein, Peter, Smits, Saskia L., Schipper, Debby, Bestebroer, Theo M, Okba, Nisreen, Fux, Robert, Bensaid, Albert, Solanes Foz, David, Kuiken, Thijs, Baumgärtner, Wolfgang, Segalés, Joaquim, Sutter, Gerd, Osterhaus, Albert D M E, Haagmans, Bart L, van den Brand, Judith M A, Raj, V Stalin, Volz, Asisa, Wohlsein, Peter, Smits, Saskia L., Schipper, Debby, Bestebroer, Theo M, Okba, Nisreen, Fux, Robert, Bensaid, Albert, Solanes Foz, David, Kuiken, Thijs, Baumgärtner, Wolfgang, Segalés, Joaquim, Sutter, Gerd, and Osterhaus, Albert D M E

Published
2016

40. Spatiotemporal Analysis of the Genetic Diversity of Seal Influenza A(H10N7) Virus, Northwestern Europe

Author

Schultz-Cherry, S., Bodewes, Rogier, Zohari, Siamak, Krog, Jesper Schak, Hall, Matthew D, Harder, Timm C, Bestebroer, Theo M, van de Bildt, Marco W G, Spronken, Monique I, Larsen, L. E., Siebert, Ursula, Wohlsein, Peter, Puff, Christina, Seehusen, Frauke, Baumgärtner, Wolfgang, Härkönen, Tero, Smits, Saskia L, Herfst, Sander, Osterhaus, Albert D M E, Fouchier, Ron A M, Koopmans, Marion P, Kuiken, Thijs, Schultz-Cherry, S., Bodewes, Rogier, Zohari, Siamak, Krog, Jesper Schak, Hall, Matthew D, Harder, Timm C, Bestebroer, Theo M, van de Bildt, Marco W G, Spronken, Monique I, Larsen, L. E., Siebert, Ursula, Wohlsein, Peter, Puff, Christina, Seehusen, Frauke, Baumgärtner, Wolfgang, Härkönen, Tero, Smits, Saskia L, Herfst, Sander, Osterhaus, Albert D M E, Fouchier, Ron A M, Koopmans, Marion P, and Kuiken, Thijs

Abstract

Influenza A viruses are major pathogens for humans, domestic animals, and wildlife, and these viruses occasionally cross the species barrier. In spring 2014, increased mortality of harbor seals (Phoca vitulina), associated with infection with an influenza A(H10N7) virus, was reported in Sweden and Denmark. Within a few months, this virus spread to seals of the coastal waters of Germany and the Netherlands, causing the death of thousands of animals. Genetic analysis of the hemagglutinin (HA) and neuraminidase (NA) genes of this seal influenza A(H10N7) virus revealed that it was most closely related to various avian influenza A(H10N7) viruses. The collection of samples from infected seals during the course of the outbreak provided a unique opportunity to follow the adaptation of the avian virus to its new seal host. Sequence data for samples collected from 41 different seals from four different countries between April 2014 and January 2015 were obtained by Sanger sequencing and next-generation sequencing to describe the molecular epidemiology of the seal influenza A(H10N7) virus. The majority of sequence variation occurred in the HA gene, and some mutations corresponded to amino acid changes not found in H10 viruses isolated from Eurasian birds. Also, sequence variation in the HA gene was greater at the beginning than at the end of the epidemic, when a number of the mutations observed earlier had been fixed. These results imply that when an avian influenza virus jumps the species barrier from birds to seals, amino acid changes in HA may occur rapidly and are important for virus adaptation to its new mammalian host. Influenza A viruses are major pathogens for humans, domestic animals, and wildlife. In addition to the continuous circulation of influenza A viruses among various host species, cross-species transmission of influenza A viruses occurs occasionally. Wild waterfowl and shorebirds are the main reservoir for most influenza A virus subtypes, and spillover of infl

Published
2016

41. Virus genomes reveal the factors that spread and sustained the West African Ebola epidemic

Author

Dudas, Gytis, primary, Carvalho, Luiz Max, additional, Bedford, Trevor, additional, Tatem, Andrew J., additional, Baele, Guy, additional, Faria, Nuno, additional, Park, Daniel J., additional, Ladner, Jason, additional, Arias, Armando, additional, Asogun, Danny, additional, Bielejec, Filip, additional, Caddy, Sarah, additional, Cotten, Matt, additional, Dambrozio, Jonathan, additional, Dellicour, Simon, additional, Di Caro, Antonino, additional, Diclaro, Joseph W., additional, Duraffour, Sophie, additional, Elmore, Mike, additional, Fakoli, Lawrence, additional, Gilbert, Merle, additional, Gevao, Sahr M., additional, Gire, Stephen, additional, Gladden-Young, Adrianne, additional, Gnirke, Andreas, additional, Goba, Augustine, additional, Grant, Donald S., additional, Haagmans, Bart, additional, Hiscox, Julian A., additional, Jah, Umaru, additional, Kargbo, Brima, additional, Kugelman, Jeffrey, additional, Liu, Di, additional, Lu, Jia, additional, Malboeuf, Christine M., additional, Mate, Suzanne, additional, Matthews, David A., additional, Matranga, Christian B., additional, Meredith, Luke, additional, Qu, James, additional, Quick, Joshua, additional, Pas, Susan D., additional, Phan, My VT, additional, Poliakis, Georgios, additional, Reusken, Chantal, additional, Sanchez-Lockhart, Mariano, additional, Schaffner, Stephen F., additional, Schieffelin, John S., additional, Sealfon, Rachel S., additional, Simon-Loriere, Etienne, additional, Smits, Saskia L., additional, Stoecker, Kilian, additional, Thorne, Lucy, additional, Tobin, Ekaete A., additional, Vandi, Mohamed A., additional, Watson, Simon J., additional, West, Kendra, additional, Whitmer, Shannon, additional, Wiley, Michael R., additional, Winnicki, Sarah M., additional, Wohl, Shirlee, additional, Wölfel, Roman, additional, Yozwiak, Nathan L., additional, Andersen, Kristian G., additional, Blyden, Sylvia, additional, Bolay, Fatorma, additional, Carroll, Miles, additional, Dahn, Bernice, additional, Diallo, Boubacar, additional, Formenty, Pierre, additional, Fraser, Christophe, additional, Gao, George F., additional, Garry, Robert F., additional, Goodfellow, Ian, additional, Günther, Stephan, additional, Happi, Christian, additional, Holmes, Edward C, additional, Kellam, Paul, additional, Koopmans, Marion P.G., additional, Loman, Nicholas J., additional, Magassouba, N’Faly, additional, Naidoo, Dhamari, additional, Nichol, Stuart T., additional, Nyenswah, Tolbert, additional, Palacios, Gustavo, additional, Pybus, Oliver G, additional, Sabeti, Pardis, additional, Sall, Amadou, additional, Sakoba, Keïta, additional, Ströeher, Ute, additional, Wurie, Isatta, additional, Suchard, Marc A, additional, Lemey, Philippe, additional, and Rambaut, Andrew, additional

Published
2016
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44. Recovering full-length viral genomes from metagenomes

Author

Smits, Saskia L, Bodewes, Rogier, Ruiz-González, Aritz, Baumgärtner, Wolfgang, Koopmans, Marion P, Osterhaus, Albert D M E, Schürch, Anita C, Smits, Saskia L, Bodewes, Rogier, Ruiz-González, Aritz, Baumgärtner, Wolfgang, Koopmans, Marion P, Osterhaus, Albert D M E, and Schürch, Anita C

Abstract

Infectious disease metagenomics is driven by the question: "what is causing the disease?" in contrast to classical metagenome studies which are guided by "what is out there?" In case of a novel virus, a first step to eventually establishing etiology can be to recover a full-length viral genome from a metagenomic sample. However, retrieval of a full-length genome of a divergent virus is technically challenging and can be time-consuming and costly. Here we discuss different assembly and fragment linkage strategies such as iterative assembly, motif searches, k-mer frequency profiling, coverage profile binning, and other strategies used to recover genomes of potential viral pathogens in a timely and cost-effective manner.

Published
2015

45. Virus characterization and discovery in formalin-fixed paraffin-embedded tissues

Author

LS GZ Landbouwhuisdieren, Bedrijfsvoering, dFAH I&I, Infection & Immunity, Bodewes, Rogier, van Run, Peter R W A, Schürch, Anita C, Koopmans, Marion P G, Osterhaus, Albert D M E, Baumgärtner, Wolfgang, Kuiken, Thijs, Smits, Saskia L, LS GZ Landbouwhuisdieren, Bedrijfsvoering, dFAH I&I, Infection & Immunity, Bodewes, Rogier, van Run, Peter R W A, Schürch, Anita C, Koopmans, Marion P G, Osterhaus, Albert D M E, Baumgärtner, Wolfgang, Kuiken, Thijs, and Smits, Saskia L

Published
2015

46. Recovering full-length viral genomes from metagenomes

Author

LS GZ Landbouwhuisdieren, Bedrijfsvoering, FAH SIB, Infection & Immunity, Smits, Saskia L, Bodewes, Rogier, Ruiz-González, Aritz, Baumgärtner, Wolfgang, Koopmans, Marion P, Osterhaus, Albert D M E, Schürch, Anita C, LS GZ Landbouwhuisdieren, Bedrijfsvoering, FAH SIB, Infection & Immunity, Smits, Saskia L, Bodewes, Rogier, Ruiz-González, Aritz, Baumgärtner, Wolfgang, Koopmans, Marion P, Osterhaus, Albert D M E, and Schürch, Anita C

Published
2015

47. Asymptomatic Middle East respiratory syndrome coronavirus infection in rabbits

Author

Haagmans, Bart L, van den Brand, Judith M A, Provacia, Lisette B, Raj, V Stalin, Stittelaar, Koert J, Getu, Sarah, de Waal, Leon, Bestebroer, Theo M, Amerongen, Geert van, Verjans, Georges M G M, Fouchier, Ron A M, Smits, Saskia L., Kuiken, Thijs, Osterhaus, Albert D M E, Haagmans, Bart L, van den Brand, Judith M A, Provacia, Lisette B, Raj, V Stalin, Stittelaar, Koert J, Getu, Sarah, de Waal, Leon, Bestebroer, Theo M, Amerongen, Geert van, Verjans, Georges M G M, Fouchier, Ron A M, Smits, Saskia L., Kuiken, Thijs, and Osterhaus, Albert D M E

Published
2015

48. Identification of protein receptors for coronaviruses by mass spectrometry

Author

LS Virologie, dI&I I&I-1, Raj, V Stalin, Lamers, Mart M, Smits, Saskia L, Demmers, Jeroen A A, Mou, Huihui, Bosch, Berend-Jan, Haagmans, Bart L, Maier, Helena Jane, Bickerton, Erica, Britton, Paul, LS Virologie, dI&I I&I-1, Raj, V Stalin, Lamers, Mart M, Smits, Saskia L, Demmers, Jeroen A A, Mou, Huihui, Bosch, Berend-Jan, Haagmans, Bart L, Maier, Helena Jane, Bickerton, Erica, and Britton, Paul

Published
2015

50. Genotypic anomaly in Ebola virus strains circulating in Magazine Wharf area, Freetown, Sierra Leone, 2015

Author

Smits, Saskia, Pas, Suzan, Reusken, Chantal, Haagmans, Bart, Pertile, P, Cancedda, C, Dierberg, K, Wurie, I, Kamara, A, Kargbo, D, Caddy, SL, Arias, A, Thorne, L, Lu, J, Jah, U, Goodfellow, I, Koopmans, Marion, Smits, Saskia, Pas, Suzan, Reusken, Chantal, Haagmans, Bart, Pertile, P, Cancedda, C, Dierberg, K, Wurie, I, Kamara, A, Kargbo, D, Caddy, SL, Arias, A, Thorne, L, Lu, J, Jah, U, Goodfellow, I, and Koopmans, Marion

Abstract

The Magazine Wharf area, Freetown, Sierra Leone was a focus of ongoing Ebola virus transmission from late June 2015. Viral genomes linked to this area contain a series of 13 T to C substitutions in a 150 base pair intergenic region downstream of viral protein 40 open reading frame, similar to the Ebolavirus/H. sapienswt/SLE/2014/Makona-J0169 strain (J0169) detected in the same town in November 2014. This suggests that recently circulating viruses from Freetown descend from a J0169-like virus.

Published
2015

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