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1. Clinical and virological properties of hepatitis C virus genotype 4 infection in patients treated with different direct-acting antiviral agents

Author: Minosse C, Selleri M, Giombini E, Bartolini B, Capobianchi MR, Cerilli S, Loiacono L, Taibi C, D'Offizi G, McPhee F, and Garbuglia AR
Subjects: Hepatitis C virus genotype 4, virologic failure, population sequencing, deep sequencing, resistance-associated substitution (RAS) identification, Infectious and parasitic diseases, RC109-216
Abstract: Claudia Minosse,1,* Marina Selleri,1,* Emanuela Giombini,1 Barbara Bartolini,1 Maria Rosaria Capobianchi,1 Stefano Cerilli,2 Laura Loiacono,2 Chiara Taibi,2 Gianpiero D’Offizi,2 Fiona McPhee,3 AnnaRosa Garbuglia1 1Department of Pre-clinical Research Epidemiology and Advanced Diagnostics, Laboratory of Virology, National Institute for Infectious Diseases “Lazzaro Spallanzani” – IRCCS, Rome, Italy; 2Clinical Department, Infectious Disease-Hepatology Unit, National Institute for Infectious Diseases, “Lazzaro Spallanzani” – IRCCS, Rome, Italy; 3Bristol-Myers Squibb Research and Development, Wallingford, CT, USA *These authors contributed equally to this work Background: The efficacy of direct-acting antivirals (DAAs) depends on the hepatitis C virus (HCV) genotype 4 (GT4) subtype which are used in the treatment of HCV. We aimed to retrospectively investigate the baseline prevalence of HCV NS5A and NS5B polymorphisms and their impact on virological outcome in GT4-infected patients treated with various DAA regimens.Patients and methods: Available plasma samples from HCV GT4-infected patients treated with different DAA regimens were analyzed at baseline and after treatment failure, where applicable. Sanger sequencing of patient-derived NS5A and NS5B regions was performed on all available samples, while ultradeep pyrosequencing (UDPS) of NS5A and NS5B regions was performed only on samples from treatment failures at different time points.Results: Sustained virological response (SVR) was achieved by 96% (48/50) of patients. Of 16 patients with baseline NS5A sequence, polymorphisms at amino acid positions associated with drug resistance were detected only at position 58: P58 (69.2%) and T58 (30.8%). Of 21 patients with baseline NS5B sequence, N142S was detected only in the two treatment failures, both with GT4d were treated with sofosbuvir (SOF)-based regimens, suggesting a potential involvement in SOF efficacy. Two patients (patient 1 [Pt1] and patient 2 [Pt2]) relapsed. In Pt1, NS5A-T56I and NS5A-Y93H/S emerged. In Pt2, NS5A-L28F emerged and a novel NS5B resistance-associated substitution (RAS), L204F, representing 1.5% of the viral population at baseline, enriched to 71% and 91.6% during and after treatment failure, respectively. UDPS of NS5B from Pt2 indicated a mixed infection of approximately 1:5, GT1a:GT4d, at baseline and GT4d during failure. Phylogenetic analysis of NS5A sequences indicated no clustering of HCV strains from patients achieving SVR vs patients who relapsed. The mean genetic distance in NS5A sequences was 5.8%, while a lower genetic distance (3.1%) was observed in NS5B sequences.Conclusion: Results from these analyses confirm the importance of UDPS in the analysis of viral quasispecies variability and the identification of novel RASs potentially associated with DAA treatment failure in HCV GT4-infected patients. Keywords: hepatitis C virus genotype 4, virological failure, population sequencing, deep sequencing, resistance-associated substitution, RAS, identification
Published: 2018

2. Safety of COVID-19 Vaccines Among the Paediatric Population: Analysis of the European Surveillance Systems and Pivotal Clinical Trials

Author: Ahmadizar F., Luxi N., Raethke M., Schmikli S., Riefolo F., Saraswati P. W., Bucsa C., Osman A., Liddiard M., Maques F. B., Petrelli G., Sonderlichova S., Thurin N. H., Villalobos F., Trifiro G., Sturkenboom M., Moretti U., Bellitto C., Ciccimarra F., Gonella L. A., Arzenton E., Chiamulera C., Lora R., Bellantuono D., Sabaini A., Firenze A., Zodda D., Guidotti F., Zappone M., Alagna B., Cutroneo P. M., Minore C., Costantino C., Vitale F., D'Alessandro G., Morreale I., Marsala L., Farinella D., Bavetta S., Fantini M. P., Reno C., Raschi E., Poluzzi E., Sapigni E., Potenza A. M., Podetti D., Nikitina V., Ricciardelli R., Mogheiseh N., Croce S., Paltrinieri B., Castellani S., Sangiorgi E., Selleri M., Lucchesi S., Catucci G., Savini D., Sacripanti C., Faccioli M., Romio M. S., Rossi L., Radici S., Negri G., Fares L., Ajolfi C., Fadda A., Chiarello A., Pieraccini F., Gavioli B., Palazzi S., Tuccori M., Vannacci A., Bonaiuti R., Ravaldi C., Lombardi N., Crescioli G., Gori F., Tessari R., Zandona E., Zanoni G., Senna G., Crivellaro M. A., Cancian M., Venturini F., Ferri M., Leonardi L., Orzetti S., Caccin E., Baldo P., Capuano A., Rafaniello C., Ferrajolo C., Pagliaro C., Mercaldo M., di Giorgio A., Tari M., Manna S., Farina G., Di Mauro C., De Carlo I., Senesi I., Pileggi C., Palleria C., Gallelli L., De Sarro G., de Sarro C., Verduci C., Papadopoli R., Trabace L., Morgese M., Schiavone S., Tucci P., Bove M., Lapi F., Cricelli C., Racagni G., Tonolo S., Fava G., Giuffrida S., Amato V., Gambera M., Montresor V., Mastropasqua D., Ahmadizar F., Luxi N., Raethke M., Schmikli S., Riefolo F., Saraswati P.W., Bucsa C., Osman A., Liddiard M., Maques F.B., Petrelli G., Sonderlichova S., Thurin N.H., Villalobos F., Trifiro G., Sturkenboom M., Moretti U., Bellitto C., Ciccimarra F., Gonella L.A., Arzenton E., Chiamulera C., Lora R., Bellantuono D., Sabaini A., Firenze A., Zodda D., Guidotti F., Zappone M., Alagna B., Cutroneo P.M., Minore C., Costantino C., Vitale F., D'Alessandro G., Morreale I., Marsala L., Farinella D., Bavetta S., Fantini M.P., Reno C., Raschi E., Poluzzi E., Sapigni E., Potenza A.M., Podetti D., Nikitina V., Ricciardelli R., Mogheiseh N., Croce S., Paltrinieri B., Castellani S., Sangiorgi E., Selleri M., Lucchesi S., Catucci G., Savini D., Sacripanti C., Faccioli M., Romio M.S., Rossi L., Radici S., Negri G., Fares L., Ajolfi C., Fadda A., Chiarello A., Pieraccini F., Gavioli B., Palazzi S., Tuccori M., Vannacci A., Bonaiuti R., Ravaldi C., Lombardi N., Crescioli G., Gori F., Tessari R., Zandona E., Zanoni G., Senna G., Crivellaro M.A., Cancian M., Venturini F., Ferri M., Leonardi L., Orzetti S., Caccin E., Baldo P., Capuano A., Rafaniello C., Ferrajolo C., Pagliaro C., Mercaldo M., di Giorgio A., Tari M., Manna S., Farina G., Di Mauro C., De Carlo I., Senesi I., Pileggi C., Palleria C., Gallelli L., De Sarro G., de Sarro C., Verduci C., Papadopoli R., Trabace L., Morgese M., Schiavone S., Tucci P., Bove M., Lapi F., Cricelli C., Racagni G., Tonolo S., Fava G., Giuffrida S., Amato V., Gambera M., Montresor V., and Mastropasqua D.
Subjects: COVID-19 Vaccines, safety, Surveillance Systems, Pivotal Clinical Trials
Abstract: Background and Objectives: The European Medicine Agency extended the use of Comirnaty, Spikevax, and Nuvaxovid in paediatrics; thus, these vaccines require additional real-world safety evidence. Herein, we aimed to monitor the safety of COVID-19 vaccines through Covid-19 Vaccine Monitor (CVM) and EudraVigilance surveillance systems and the published pivotal clinical trials. Methods: In a prospective cohort of vaccinees aged between 5 and 17 years, we measured the frequency of commonly reported (local/systemic solicited) and serious adverse drug events (ADRs) following the first and second doses of COVID-19 vaccines in Europe using data from the CVM cohort until April 2022. The results of previous pivotal clinical trials and data in the EudraVigilance were also analysed. Results: The CVM study enrolled 658 first-dose vaccinees (children aged 5–11 years; n = 250 and adolescents aged 12–17 years; n = 408). Local/systemic solicited ADRs were common, whereas serious ADRs were uncommon. Among Comirnaty first and second dose recipients, 28.8% and 17.1% of children and 54.2% and 52.2% of adolescents experienced at least one ADR, respectively; injection-site pain (29.2% and 20.7%), fatigue (16.1% and 12.8%), and headache (22.1% and 19.3%) were the most frequent local and systemic ADRs. Results were consistent but slightly lower than in pivotal clinical trials. Reporting rates in Eudravigilance were lower by a factor of 1000. Conclusions: The CVM study showed high frequencies of local solicited reactions after vaccination but lower rates than in pivotal clinical trials. Injection-site pain, fatigue, and headache were the most commonly reported ADRs for clinical trials, but higher than spontaneously reported data.
Published: 2023

3. Quasispecies tropism and compartmentalization in gut and peripheral blood during early and chronic phases of HIV-1 infection: possible correlation with immune activation markers

Author: Rozera, G., Abbate, I., Vlassi, C., Giombini, E., Lionetti, R., Selleri, M., Zaccaro, P., Bartolini, B., Corpolongo, A., D’Offizi, G., Baiocchini, A., Del Nonno, F., Ippolito, G., and Capobianchi, M.R.
Published: 2014
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4. Detection of haemagglutinin D222 polymorphisms in influenza A(H1N1)pdm09-infected patients by ultra-deep pyrosequencing

Author: Selleri, M., Piralla, A., Rozera, G., Giombini, E., Bartolini, B., Abbate, I., Campanini, G., Rovida, F., Dossena, L., Capobianchi, M.R., and Baldanti, F.
Published: 2013
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5. Dynamics and phylogenetic relationships of HIV-1 transmitted drug resistance according to subtype in Italy over the years 2000–14

Author: Fabeni, L., Alteri, C., Di Carlo, D., Orchi, N., Carioti, L., Bertoli, A., Gori, C., Forbici, F., Continenza, F., Maffongelli, G., Pinnetti, C., Vergori, A., Mondi, A., Ammassari, A., Borghi, V., Giuliani, M., De Carli, G., Pittalis, S., Grisetti, S., Pennica, A., Mastroianni, C. M., Montella, F., Cristaudo, A., Mussini, C., Girardi, E., Andreoni, M., Antinori, A., Ceccherini-Silberstein, F., Perno, C. F., Santoro, M. M., Girardi, E., Capobianchi, M. R., Perno, C. F., Orchi, N., Navarra, A., Palummieri, A., Abbate, I., Ammassari, A., D’Arrigo, R., De Carli, G., Fabeni, L., Forbici, F., Fusco, F. M., Gori, C., Grisetti, S., Mariano, A., Nicastri, E., Nurra, G., Pinnetti, C., Pittalis, S., Puro, V., Sampaolesi, A., Sciarrone, M. R., Scognamiglio, P., Selleri, M., Sias, C., Zaccarelli, M., Di Carlo, A., Giuliani, M., Vullo, V., Falciano, M., Pennica, A., Errigo, F., Gattari, P., Spizzichino, L., Schito, S., Andreoni, M., Sarmati, L., Buonomini, A. R., Cerva, C., Mastroianni, C., Lichtner, M., Mercurio, V. S., Anzalone, E., Pitorri, A., Caterini, A., and Barbacci, S. Aviani
Published: 2017
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6. COVID-19 Vaccination in Pregnancy, Paediatrics, Immunocompromised Patients, and Persons with History of Allergy or Prior SARS-CoV-2 Infection: Overview of Current Recommendations and Pre- and Post-Marketing Evidence for Vaccine Efficacy and Safety

Author: Luxi N., Giovanazzi A., Capuano A., Crisafulli S., Cutroneo P. M., Fantini M. P., Ferrajolo C., Moretti U., Poluzzi E., Raschi E., Ravaldi C., Reno C., Tuccori M., Vannacci A., Zanoni G., Trifiro G., Petrelli G., Girotti S., Arzenton E., Magro L., Lora R., Bellantuono D., Sabaini A., Firenze A., Zodda D., Guidotti F., Zappone M., Alagna B., Spina E., Minore C., Costantino C., Conforto A., Vitale F., Morreale I., Marsala L., Farinella D., Bavetta S., Sapigni E., Potenza A. M., Podetti D., Nikitina V., Ricciardelli R., Mogheiseh N., Croce S., Paltrinieri B., Castellani S., Sangiorgi E., Selleri M., Lucchesi S., Catucci G., Savini D., Sacripanti C., Faccioli M., Romio M. S., Rossi L., Radici S., Negri G., Fares L., Ajolfi C., Fadda A., Chiarello A., Pieraccini F., Pappalardo F., Bonaiuti R., Lombardi N., Crescioli G., Tessari R., Zandona E., Marchiori F., Chiamulera C., Senna G., Crivellaro M. A., Cancian M., Venturini F., Ferri M., Leonardi L., Orzetti S., Caccin E., Baldo P., Rafaniello C., Pagliaro C., Mercaldo M., Fucile A., di Giorgio A., Tari M., Manna S., Farina G., Di Mauro C., De Carlo I., Senesi I., Pileggi C., Palleria C., Gallelli L., De Sarro G., Trabace L., Morgese M., Schiavone S., Tucci P., Bove M., Lapi F., Cricelli C., Racagni G., Tonolo S., Leopardi E., Fava G., Giuffrida S., Amato V., Gambera M., Montresor V., Luxi N., Giovanazzi A., Capuano A., Crisafulli S., Cutroneo P.M., Fantini M.P., Ferrajolo C., Moretti U., Poluzzi E., Raschi E., Ravaldi C., Reno C., Tuccori M., Vannacci A., Zanoni G., Trifiro G., Luxi, N., Giovanazzi, A., Capuano, A., Crisafulli, S., Cutroneo, P. M., Fantini, M. P., Ferrajolo, C., Moretti, U., Poluzzi, E., Raschi, E., Ravaldi, C., Reno, C., Tuccori, M., Vannacci, A., Zanoni, G., Trifiro, G., Petrelli G., Girotti S., Arzenton E., Magro L., Lora R., Bellantuono D., Sabaini A., Firenze A., Zodda D., Guidotti F., Zappone M., Alagna B., Spina E., Minore C., Costantino C., Conforto A., Vitale F., Morreale I., Marsala L., Farinella D., Bavetta S., Sapigni E., Potenza A.M., Podetti D., Nikitina V., Ricciardelli R., Mogheiseh N., Croce S., Paltrinieri B., Castellani S., Sangiorgi E., Selleri M., Lucchesi S., Catucci G., Savini D., Sacripanti C., Faccioli M., Romio M.S., Rossi L., Radici S., Negri G., Fares L., Ajolfi C., Fadda A., Chiarello A., Pieraccini F., Pappalardo F., Bonaiuti R., Lombardi N., Crescioli G., Tessari R., Zandona E., Marchiori F., Chiamulera C., Senna G., Crivellaro M.A., Cancian M., Venturini F., Ferri M., Leonardi L., Orzetti S., Caccin E., Baldo P., Rafaniello C., Pagliaro C., Mercaldo M., Fucile A., di Giorgio A., Tari M., Manna S., Farina G., Di Mauro C., De Carlo I., Senesi I., Pileggi C., Palleria C., Gallelli L., De Sarro G., Trabace L., Morgese M., Schiavone S., Tucci P., Bove M., Lapi F., Cricelli C., Racagni G., Tonolo S., Leopardi E., Fava G., Giuffrida S., Amato V., Gambera M., and Montresor V.
Subjects: Allergy, IMPACT, COVID-19 Vaccine, Breastfeeding, Review Article, Toxicology, Settore MED/42 - Igiene Generale E Applicata, CLINICAL CHARACTERISTICS, Pregnancy, Pharmacology (medical), Pregnancy Complications, Infectious, Child, OUTCOMES, education.field_of_study, CANCER, Vaccination, Europe, CORONAVIRUS DISEASE 2019, CLINICAL CHARACTERISTICS, CANCER, RECIPIENTS, SEVERITY, OUTCOMES, IMPACT, RATES, Breast Feeding, Child, Preschool, Practice Guidelines as Topic, Female, 2019-nCoV Vaccine mRNA-1273, Human, Adult, medicine.medical_specialty, COVID-19 Vaccines, Adolescent, BNT162 Vaccine, COVID-19, ChAdOx1 nCoV-19, Humans, Infant, SARS-CoV-2, Hypersensitivity, Immunocompromised Host, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Population, MEDLINE, CORONAVIRUS DISEASE 2019, medicine, RATES, education, Pharmacology, business.industry, medicine.disease, Vaccine efficacy, RECIPIENTS, SEVERITY, Family medicine, Pregnancy Complications, Infectiou, business
Abstract: To date, four vaccines have been authorised for emergency use and under conditional approval by the European Medicines Agency to prevent COVID-19: Comirnaty, COVID-19 Vaccine Janssen, Spikevax (previously COVID-19 Vaccine Moderna) and Vaxzevria (previously COVID-19 Vaccine AstraZeneca). Although the benefit–risk profile of these vaccines was proven to be largely favourable in the general population, evidence in special cohorts initially excluded from the pivotal trials, such as pregnant and breastfeeding women, children/adolescents, immunocompromised people and persons with a history of allergy or previous SARS-CoV-2 infection, is still limited. In this narrative review, we critically overview pre- and post-marketing evidence on the potential benefits and risks of marketed COVID-19 vaccines in the above-mentioned special cohorts. In addition, we summarise the recommendations of the scientific societies and regulatory agencies about COVID-19 primary prevention in the same vaccinee categories. Supplementary Information The online version contains supplementary material available at 10.1007/s40264-021-01131-6.
Published: 2021

7. Markers of human papillomavirus infection and their correlation with cervical dysplasia in human immunodeficiency virus-positive women

Author: Riva, E., Serraino, D., Pierangeli, A., Bambacioni, F., Zaniratti, S., Minosse, C., Selleri, M., Bucci, M., Scagnolari, C., Degener, A.M., Capobianchi, M.R., Antonelli, G., and Dianzani, F.
Published: 2007
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8. High prevalence of rhinovirus in lower respiratory tract specimens: P1325

Author: Minosse, C., Selleri, M., Zaniratti, S., Cappiello, G., Lauria, F. N., Longo, R., Roselli, P., Antonelli, S., Schifano, E., Visca, M., Cava, M., Spanò, A., Capobianchi, M. R., and Puro, V.
Published: 2005

9. In-depth analysis of compartmentalization of HIV-1 matrix protein p17 in PBMC and plasma

Author: Selleri, M., Dolcetti, R., Caccuri, F., Giombini, E., Rozera, G., Abbate, I., Mammone, A., Zanussi, S., Martorelli, D., SIMONA FIORENTINI, Caruso, A., and Capobianchi, M. R.
Subjects: Ultra-deep pyrosequencing, Gene Expression Regulation, Viral, HIV Antigens, p17, HIV Infections, gag Gene Products, Human Immunodeficiency Virus, Viral quasispecies, HIV-1 matrix protein, Compartmentalization, HIV-1, Leukocytes, Mononuclear, Humans, Non-Hodgkin lymphoma, Phylogeny
Abstract: HIV-1 p17 plays an important role in the virus life-cycle and disease pathogenesis. Recent studies indicated a high heterogeneity of p17. A high number of insertions in the p17 carboxy-terminal region have been more frequently detected in patients with non-Hodgkin lymphoma (NHL), suggesting a role of altered p17 in lymphomagenesis. Based on p17 heterogeneity, possible PBMC/plasma compartmentalization of p17 variants was explored by ultra-deep pyrosequencing in five NHL patients. The high variability of p17 with insertions at the carboxy-terminal region was confirmed in plasma and observed for the first time in proviral genomes. Quasispecies compartmentalization was evident in 4/5 patients. Further studies are needed to define the possible role of p17 quasispecies compartmentalization in lymphomagenesis.
Published: 2017

10. The potential impact of routine testing of individuals with HIV indicator diseases in order to prevent late HIV diagnosis

Author: Scognamiglio, Paola, Chiaradia, Giacomina, De Carli, Gabriella, Giuliani, Massimo, Mastroianni, Claudio Maria, Aviani Barbacci, Stefano, Buonomini, Anna R., Grisetti, Susanna, Sampaolesi, Alessandro, Corpolongo, Angela, Orchi, Nicoletta, Puro, Vincenzo, Ippolito, Giuseppe, Girardi, Enrico, Girardi, E., Orchi, N., Angeletti, C., Balzano, R., Elia, P., Navarra, A., Nurra, G., Palummieri, A., Alba, L., Ammassari, A., Antinori, A., Baldini, F., Bellagamba, R., Bevilacqua, N., Boumis, E., Capobianchi, M. R., Cerilli, S., Chinello, P., Corpolongo, A., D'Arrigo, R., De Carli, G., Null, D'Offizig, Forbici, F., Fusco, F. M., Galati, V., Ghirga, P., Giancola, L., Gori, C., Grisetti, S., Lauria, F. N., Liuzzi, G., Marconi, P., Mariano, A., Narciso, P., Nicastri, E., Noto, P., Palmieri, A. F., Perno, C. F., Petrosillo, N., Pisapia, R., Pittalis, S., Puro, V., Sampaolesi, A., Scognamiglio, P., Sciarrone, M. R., Selleri, M., Sias, C., Topino, S., Tozzi, V., Vincenzi, L., Visco Comandini, U., Vlassi, C., Zaccarelli, M., Zaniratti, S., Vullo, Vincenzo, Falciano, Mario, Andreoni, M., Sarmati, L., Buonomini, A. R., Di Carlo, A., Giuliani, M., Brancatella, R., Maggi, T., Errico, F., De Filippis, A., Di Bacco, R., Schito, S., Gattari, P., Spizzichino, L., Francesconi, M., Pace, G., Gallo, I., Anzalone, E., Tacconi, L., Mercurio, V. S., Lichtner, Miriam, Natalini Raponi, G., Pitorri, A., Caterini, A., and Aviani Barbacci, S.
Subjects: Adult, Male, Pediatrics, medicine.medical_specialty, Delayed Diagnosis, Tuberculosis, Adolescent, HIV Infections, Disease, HIV testing, Indicator diseases, Late diagnosis, Sexually transmitted infections, Aged, Aged, 80 and over, CD4 Lymphocyte Count, Diagnostic Tests, Routine, Female, Humans, Italy, Middle Aged, Retrospective Studies, Risk Factors, Young Adult, Infectious Diseases, Medical microbiology, Diagnostic Tests, 80 and over, Medicine, Routine, Young adult, business.industry, virus diseases, Seborrhoeic dermatitis, Retrospective cohort study, medicine.disease, Settore MED/17, Surgery, Population study, business, Viral hepatitis, Research Article
Abstract: Background The aim of our work was to evaluate the potential impact of the European policy of testing for HIV all individuals presenting with an indicator disease, to prevent late diagnosis of HIV. We report on a retrospective analysis among individuals diagnosed with HIV to assess whether a history of certain diseases prior to HIV diagnosis was associated with the chance of presenting late for care, and to estimate the proportion of individuals presenting late who could have been diagnosed earlier if tested when the indicator disease was diagnosed. Methods We studied a large cohort of individuals newly diagnosed with HIV infection in 13 counselling and testing sites in the Lazio Region, Italy (01/01/2004-30/04/2009). Considered indicator diseases were: viral hepatitis infection (HBV/HCV), sexually transmitted infections, seborrhoeic dermatitis and tuberculosis. Logistic regression analysis was performed to estimate association of occurrence of at least one indicator disease with late HIV diagnosis. Results In our analysis, the prevalence of late HIV diagnosis was 51.3% (890/1735). Individuals reporting at least one indicator disease before HIV diagnosis (29% of the study population) had a lower risk of late diagnosis (OR = 0.7; 95%CI: 0.5-0.8) compared to those who did not report a previous indicator disease. 52/890 (5.8%) late presenters were probably already infected at the time the indicator disease was diagnosed, a median of 22.6 months before HIV diagnosis. Conclusions Our data suggest that testing for HIV following diagnosis of an indicator disease significantly decreases the probability of late HIV diagnosis. Moreover, for 5.5% of late HIV presenters, diagnosis could have been anticipated if they had been tested when an HIV indicator disease was diagnosed. However, this strategy for enhancing early HIV diagnosis needs to be complemented by client-centred interventions that aim to increase awareness in people who do not perceive themselves as being at risk for HIV.
Published: 2013

11. HBV genetic compartimentalization, variability and molecular correlates of histologic and immunohistochemical aspects in liver tissue: implications for the clinical management of patients with chronic hepatitis B

Author: Minosse, C., primary, Baiocchini, A., additional, Selleri, M., additional, Giombini, E., additional, Coen, S., additional, Zaccaro, P., additional, Rozera, G., additional, Vincenti, D., additional, Del Nonno, F., additional, Comandini, U. Visco, additional, Lionetti, R., additional, Montalbano, M., additional, D’Offizi, G., additional, Vivarelli, M., additional, Capobianchi, M.R., additional, and Menzo, S., additional
Published: 2015
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12. Characterization of the patterns of drug-resistance mutations in newly diagnosed HIV-1 infected patients naïve to the antiretroviral drugs

Author: Alteri, C, Svicher, V, Gori, C, D'Arrigo, R, Ciccozzi, M, CECCHERINI SILBERSTEIN, F, Selleri, M, Bardacci, S, Giuliani, M, Elia, P, Scognamiglio, P, Balzano, R, Orchi, N, Girardi, E, Perno, Cf, Capobianchi, M, De Carli, G, Galati, V, Grisetti, S, Navarra, A, Nicastri, E, Pittalis, S, Puro, V, Sampaolesi, A, Nurra, G, Zaccarelli, M, Zaniratti, M, Di Carlo, A, De Filippis, A, Brancatella, R, Maggi, T, Gattari, P, Spizzichino, L, Schito, S, Sarmati, L, Battagin, G, Tacconi, L, Gallo, I, Anzalone, E, Pitorri, A, Caterini, A, and Barbacci, S
Subjects: virus strain, Male, genotype, Drug Resistance, Human immunodeficiency virus 1, Etravirine, RNA directed DNA polymerase inhibitor, HIV Infections, Drug resistance, RNA directed DNA polymerase, HIV Antibodies, Cohort Studies, Medical microbiology, binding affinity, Prevalence, HIV Protease Inhibitor, genetics, Viral, Phylogeny, virus mutation, drug effect, article, virus diseases, homosexuality, Middle Aged, cohort analysis, Infectious Diseases, Italy, virus resistance, Cohort, RNA, Viral, Reverse Transcriptase Inhibitors, proteinase, Female, Research Article, medicine.drug, Cohort study, Adult, medicine.medical_specialty, Settore MED/17 - Malattie Infettive, Evolution, proteinase inhibitor, Human immunodeficiency virus antibody, virus RNA, adult, antiviral resistance, codon, DNA polymorphism, female, human, Human immunodeficiency virus 1 infection, major clinical study, male, phylogeny, prevalence, virus carrier, virus load, blood, Human immunodeficiency virus infection, middle aged, molecular evolution, mutation, sequence alignment, statistical model, Drug Resistance, Viral, Evolution, Molecular, HIV Protease Inhibitors, HIV-1, Humans, Logistic Models, Mutation, Sequence Alignment, Biology, lcsh:Infectious and parasitic diseases, medicine, lcsh:RC109-216, Molecular, Virology, Reverse transcriptase, Drug-naïve, Immunology, RNA
Abstract: BackgroundThe transmission of HIV-1 drug-resistant strains in drug naive patients may seriously compromise the efficacy of a first-line antiretroviral treatment. To better define this problem, a study in a cohort of newly diagnosed HIV-1 infected individuals has been conducted. This study is aimed to assess the prevalence and the patterns of the mutations recently associated with transmitted drug resistance in the reverse transcriptase (RT) and in protease (PR) of HIV-1.MethodsPrevalence of transmitted drug resistant strains is determined in 255 newly diagnosed HIV-1 infected patients enrolled in different counselling and testing (CT) centres in Central Italy; the Avidity Index (AI) on the first available serum sample is also used to estimate time since infection. Logistic regression models are used to determine factors associated with infection by drug resistant HIV-1 strains.ResultsThe prevalence of HIV-1 strains with at least one major drug resistance mutation is 5.9% (15/255); moreover, 3.9% (10/255) of patients is infected with HIV nucleoside reverse transcriptase inhibitor (NRTI)-resistant viruses, 3.5% (9/255) with HIV non-NRTI-resistant viruses and 0.4% (1/255) with HIV protease inhibitor (PI)-resistant viruses. Most importantly, almost half (60.0%) of patients carries HIV-1 resistant strains with more than one major drug resistance mutation. In addition, patients who had acquired HIV through homosexual intercourses are more likely to harbour a virus with at least one primary resistance mutation (OR 7.7; 95% CI: 1.7–35.0, P = 0.008).ConclusionThe prevalence of drug resistant HIV-1 strains among newly diagnosed individuals in Central Italy is consistent with the data from other European countries. Nevertheless, the presence of drug-resistance HIV-1 mutations in complex patterns highlights an additional potential risk for public health and strongly supports the extension of wide genotyping to newly diagnosed HIV-1 infected patients.
Published: 2009

13. Clinical features and therapeutic management of patients admitted to Italian acute hospital psychiatric units: the PERSEO (psychiatric emergency study and epidemiology) survey

Author: Ballerini, Andrea, Boccalon, Roberto M., Boncompagni, Giancarlo, Casacchia, Massimo, Margari, Francesco, Minervini, Lina, Righi, Roberto, Russo, Federico, Salteri, Andrea, Frediani, Sonia, Rossi, Andrea, Scatigna, Marco, Barale, F., Bonzano, A., Scioli, R., Bellomo, A., De Giorgi, A., Cammeo, C., Cao, A., Zara, B., Conforti, I., Chillemi, C., Dagnino, L., Ponzoni, M., Della Pietra, F., Benettazzo, M., Esposito, V., Sposito, M., Fato, M., Signorello, G., Fiorenzoni, S., Singali, A., Margari, F., Sicolo, M., Martino, C., Leria, G., Tavoaccini, L., Nigro, G., Russo, V., La Roere, R., Righi, R., Mazzo, M., Rocchetti, R., De Martiis, L., Rodighiero, S., Morello, M., Vescera, M., Pisciotti, D. G., Villari, V., Barzegna, G., Annicchiarico, V., Cosmai, M. G., Rossi, G., Baraldi, E. C., Casacchia, M., Ruggiero, D., Galimberti, P., Fellini, F. A., Francobandiera, G., Gaspari, D., Turati, D., Matacchieri, B., Moscati, G., Mautone, A., DEL CASALE, Monia, Mellado, C., Scaramelli, B., Flilippo, A., Miccichè, M., Minervini, I., Banzato, C., Orengo, S., Alisio, G., Picci, R. L., Venturello, S., D'Aloise, A., Vaira, F., Boccalon, R. M., Cavrini, L., Cogrossi, S., Prato, K., Cremonese, C., Menardi, A., Parisi, M., Mentastro, C., Prosperini, P., Binda, V., Romano, G., Materzanini, A., Crudele, A., Stella, Giuseppe, Petio, C., Fuà, B., Laich, L., Miori, M., Salteri, A., Catania, G., Achena, M., Fara, F. M., Padoani, W., Compagno, S., Pecchioli, S., Moretti, S., Bacchi, L., Vicari, E., Arvizzigno, C., Minunni, P., Rossi, E., Zaiti, M. F., Boncompagni, G., Selleri, M. S., Minnai, G. P., Loche, A. P., Russo, FRANCESCA PAOLA, Antonucci, Annapaola, Chiurco, L., Amendola, R., De Giovanni, M. G., Martano, A., Borsetti, G., Santone, G., Pettolino, A. R., Lisanti, F., Parodi, A., Ciammella, L., Botto, G., Gillotta, S., Florio, G., Fiore, F., Santangelo, E., Fucci, G., Ricci, M., Ciaramella, A., Della Porta, A., Sittinieri, M., D'Asta, L., Triolo, S., Spatola, A., Frediani, S., Rossi, A., Macchi, S., Giovannini, L., Germani, S., Fabbri, Luigi, Fiori, G., Sala, S., Sgarbi, S., Simoni, L., and Zanoli, M.
Subjects: life habits and psychiatric diagnoses, Polypharmacy, Pediatrics, medicine.medical_specialty, business.industry, lcsh:RC435-571, psychiatric emergency, epidemiology, risk factors, medicine.disease, Psychiatry and Mental health, Epidemiology of child psychiatric disorders, Schizophrenia, lcsh:Psychiatry, Epidemiology, medicine, Observational study, Medical prescription, Primary Research, business, Psychiatry, Geriatric psychiatry, Depression (differential diagnoses)
Abstract: Background The PERSEO study (psychiatric emergency study and epidemiology) is a naturalistic, observational clinical survey in Italian acute hospital psychiatric units, called SPDCs (Servizio Psichiatrico Diagnosi e Cura; in English, the psychiatric service for diagnosis and management). The aims of this paper are: (i) to describe the epidemiological and clinical characteristics of patients, including sociodemographic features, risk factors, life habits and psychiatric diagnoses; and (ii) to assess the clinical management, subjective wellbeing and attitudes toward medications. Methods A total of 62 SPDCs distributed throughout Italy participated in the study and 2521 patients were enrolled over the 5-month study period. Results Almost half of patients (46%) showed an aggressive behaviour at admission to ward, but they engaged more commonly in verbal aggression (38%), than in aggression toward other people (20%). A total of 78% of patients had a psychiatric diagnosis at admission, most frequently schizophrenia (36%), followed by depression (16%) and personality disorders (14%), and no relevant changes in the diagnoses pattern were observed during hospital stay. Benzodiazepines were the most commonly prescribed drugs, regardless of diagnosis, at all time points. Overall, up to 83% of patients were treated with neuroleptic drugs and up to 27% received more than one neuroleptic either during hospital stay or at discharge. Atypical and conventional antipsychotics were equally prescribed for schizophrenia (59 vs 65% during stay and 59 vs 60% at discharge), while atypical drugs were preferred in schizoaffective psychoses (72 vs 49% during stay and 70 vs 46% at discharge) and depression (41 vs 32% during stay and 44 vs 25% at discharge). Atypical neuroleptics were slightly preferred to conventional ones at hospital discharge (52 vs 44%). Polypharmacy was in general widely used. Patient attitudes toward medications were on average positive and self-reported compliance increased during hospital stay. Conclusion Results confirm the widespread use of antipsychotics and the increasing trend in atypical drugs prescription, in both psychiatric in- and outpatients.
Published: 2007

14. MARKERS OF HPV INFECTION AND THEIR CORRELATION WITH CERVICAL DYSPLASIA IN HIV-POSITIVE WOMEN

Author: Riva, E., Serraino, D., Pierangeli, Alessandra, Bambacioni, F., Zaniratti, S., Minosse, C., Selleri, M., Bucci, Mauro, Scagnolari, Carolina, Degener, Anna Marta, Capobianchi, Mr, Antonelli, Guido, and DIANZANI AND ROMAN PAPILLOMAVIRUS STUDY GROUP, F.
Published: 2007

15. Phylogenetic analysis of human coronavirus NL63 circulating in Italy

Author: Minosse, C., Selleri, M., Zaniratti, M.S., Cappiello, G., Spanò, A., Schifano, E., Lauria, F.N., Gualano, G., Puro, V., Campanini, G., Gerna, G., and Capobianchi, M.R.
Published: 2008
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16. Frequency of detection of respiratory viruses in the lower respiratory tract of hospitalized adults

Author: Minosse, C., Selleri, M., Zaniratti, M.S., Cappiello, G., Longo, R., Schifano, E., Spanò, A., Petrosillo, N., Lauria, F.N., Puro, V., and Capobianchi, M.R.
Published: 2008
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17. Retrospective screening of solid organ donors in Italy, 2009, reveals unpredicted circulation of West Nile virus

Author: Capobianchi, M R, primary, Sambri, V, additional, Castilletti, C, additional, Pierro, A M, additional, Rossini, G, additional, Gaibani, P, additional, Cavrini, F, additional, Selleri, M, additional, Meschi, S, additional, Lapa, D, additional, Di Caro, A, additional, Grossi, P, additional, De Cillia, C, additional, Venettoni, S, additional, Landini, M P, additional, Ippolito, G, additional, Nanni Costa, A, additional, and on behalf of the Italian Transplant Network, Collective, additional
Published: 2010
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18. A case of dengue type 3 virus infection imported from Africa to Italy, October 2009

Author: Nisii, C, primary, Carletti, F, additional, Castilletti, C, additional, Bordi, L, additional, Meschi, S, additional, Selleri, M, additional, Chiappini, R, additional, Travaglini, D, additional, Antonini, M, additional, Castorina, S, additional, Lauria, F N, additional, Narciso, P, additional, Gentile, M, additional, Martini, L, additional, Di Perri, G, additional, Audagnotto, S, additional, Biselli, R, additional, Lastilla, M, additional, Di Caro, A, additional, Capobianchi, M R, additional, and Ippolito, G, additional
Published: 2010
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19. P1916 The evolution of the avidity of HIV–1–specific antibodies is prevented by early treatment started during primary HIV–1 infection

Author: Selleri, M., primary, Zaniratti, M., additional, Orchi, N., additional, Corpolongo, A., additional, Zaccaro, P., additional, Ippolito, G., additional, Capobianchi, M., additional, and Girardi, E., additional
Published: 2007
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20. IL TRATTAMENTO PRECOCE NELLE INFEZIONI ACUTE DA HIV-1 INCIDE SULLA MATURAZIONE DELLA RISPOSTA UMORALE ANTI-HIV

Author: Selleri, M., primary, Zaniratti, M.S., additional, Orchi, N., additional, Corpolongo, A., additional, Zaccaro, P., additional, Ippolito, G., additional, Capobianchi, M.R., additional, and Girardi, E., additional
Published: 2006
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21. PREVALENZA DI AGENTI RESPIRATORI IN CAMPIONI DEL TRATTO RESPIRATORIO INFERIORE DI PAZIENTI OSPEDALIZZATI

Author: Minosse, C., primary, Selleri, M., additional, Zaniratti, M.S., additional, Cappiello, G., additional, Longo, R., additional, Schifano, E., additional, Cava, M., additional, Petrosillo, N., additional, Gualano, G., additional, Spanò, A., additional, Lauria, F.N., additional, Puro, V., additional, and Capobianchi, M.R., additional
Published: 2006
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22. RILEVAZIONE DI VIRUS RESPIRATORI IN PAZIENTI CON PATOLOGIE DEL TRATTO RESPIRATORIO INFERIORE

Author: Selleri, M., primary, Minosse, C., additional, Zaniratti, M.S., additional, Cappiello, G., additional, Lauria, F.N., additional, Longo, R., additional, Roselli, P., additional, Antonelli, S., additional, Schifano, E., additional, Tana, M., additional, Visca, M., additional, Cava, M., additional, Spanò, A., additional, De Mori, P., additional, Gualano, G., additional, Capobianchi, M.R., additional, and Puro, V., additional
Published: 2005
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23. POSSIBILE COMPARTIMENTALIZZAZIONE DELLA REPLICAZIONE DI HCV IN SITI EXTRAEPATICI:ANALISI DELLA QUASI SPECIE DI HCV NELL’AREA GENITALE FEMMINILE.

Author: Minosse, C., primary, Calcaterra, S., additional, Abbate, I., additional, Selleri, M., additional, Zaniratti, M.S., additional, Pavia, C., additional, Pisani, G., additional, and Capobianchi, M.R., additional
Published: 2005
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24. Retrospective screening of solid organ donors in Italy, 2009, reveals unpredicted circulation of West Nile virus

Author: Capobianchi, Mr, Sambri, V, Castilletti, C, Pierro, Am, Rossini, G, Gaibani, P, Cavrini, F, Selleri, M, Meschi, S, Lapa, D, Di Caro, A, Grossi, P, De Cillia, C, Venettoni, S, Landini, Mp, Ippolito, G, Nanni Costa, A, Italian Transplant Network Collaborators: Scalamogna, M, Famulari, A, Saracino, A, Giacon, B, Mancini, P, Di Florio, E, Ridolfi, L, Peressutti, R, Adorno, D, Castiglione, Ag, Vesconi, S, Testasecca, D, Amoroso, Antonio, Schena, Fp, Carcassi, C, Sparacino, V, Lippi, R, Gabardi, E, Gambelunghe, C, Calabrò, F., Capobianchi M.R., Sambri V., Castilletti C., Pierro A.M., Rossini G., Gaibani P., Cavrini F., Selleri M., Meschi S., Lapa D., Di Caro A., Grossi P., De Cillia C., Venettoni S., Landini M., Ippolito G., and Nanni Costa A.
Subjects: SOLID ORGAN TRANSPLANT, Adult, organ donor, Epidemiology, West Nile virus, animal diseases, viruses, medicine.disease_cause, Virus, Flaviviridae, West nile virus, screening, transplantation, Predictive Value of Tests, Virology, medicine, Humans, Aged, Retrospective Studies, Aged, 80 and over, biology, business.industry, Transmission (medicine), SEROPREVALENCE, Public Health, Environmental and Occupational Health, virus diseases, Retrospective cohort study, Middle Aged, biology.organism_classification, Health Surveys, Tissue Donors, nervous system diseases, Transplantation, Flavivirus, Italy, Immunology, Risk assessment, business, West Nile Fever
Abstract: Since the occurrence of West Nile virus (WNV) infection in humans in 2008 in Italy, concerns have been raised about the potential risks associated with solid organ transplantation (SOT). A nationwide retrospective survey showed that 1.2% of SOT donors in 2009 were WNV-seropositive and demonstrated that human WNV infection is distributed throughout several Italian regions. Transmission of WNV or other arboviruses through SOT is a possibility and risk assessment should be carried out before SOT to avoid infection through transplantation.

25. A case of dengue type 3 virus infection imported from Africa to Italy, October 2009

Author: carla nisii, Carletti F, Castilletti C, Bordi L, Meschi S, Selleri M, Chiappini R, Travaglini D, Antonini M, Castorina S, Fn, Lauria, Narciso P, Gentile M, Martini L, Di Perri G, Audagnotto S, Biselli R, Lastilla M, Di Caro A, and Capobianchi M

26. SARS-CoV-2 Serum Neutralization Assay: A Traditional Tool for a Brand-New Virus

Author: Matusali G., Colavita F., Lapa D., Meschi S., Bordi L., Piselli P., Gagliardini R., Corpolongo A., Nicastri E., Antinori A., Ippolito G., Capobianchi M. R., Castilletti C., Abbate I., Agrati C., Aleo L., Alonzi T., Amendola A., Apollonio C., Arduini N., Bartolini B., Berno G., Biancone S., Bibbo A., Brega C., Canali M., Cannas A., Carletti F., Carrara S., Casetti R., Castillettiy C., Chiappini R., Ciafrone L., Cimini E., Coen S., Condello R., Coppola A., D'arezzo S., Di Caro A., Di Filippo S., De Giuli C., Fabeni L., Felici L., Ferraioli V., Forbici F., Garbuglia A. R., Giombini E., Gruber C. E. M., Khouri D., Lalle E., Leone B., Mazzarelli A., Messina F., Minosse C., Montaldo C., Neri S., Nisii C., Petrivelli E., Petroni F., Petruccioli E., Pisciotta M., Pizzi D., Prota G., Rozera G., Rueca M., Sabatini R., Sarti S., Sberna G., Sciamanna R., Selleri M., Selvaggi C., Stellitano C., Toffoletti A., Truffa S., Turchi F., Valli M. B., Venditti C., Vincenti D., Vulcano A., Zambelli E., Bevilacqua N., Bordoni V., D'abramo A., Lepore L., Mariano A., Palazzolo C., Lorenzini P., Notari S., Sacchi A., Scorzolini L., Bettini A., Francalancia M., Specchiarello E., Federica M., Gaetano D., Luigi F., Barbara G., Roberto I., Giovanni M., Mirco M., Rachele S., Matusali, G., Colavita, F., Lapa, D., Meschi, S., Bordi, L., Piselli, P., Gagliardini, R., Corpolongo, A., Nicastri, E., Antinori, A., Ippolito, G., Capobianchi, M. R., Castilletti, C., Abbate, I., Agrati, C., Aleo, L., Alonzi, T., Amendola, A., Apollonio, C., Arduini, N., Bartolini, B., Berno, G., Biancone, S., Bibbo, A., Brega, C., Canali, M., Cannas, A., Carletti, F., Carrara, S., Casetti, R., Castillettiy, C., Chiappini, R., Ciafrone, L., Cimini, E., Coen, S., Condello, R., Coppola, A., D'Arezzo, S., Di Caro, A., Di Filippo, S., De Giuli, C., Fabeni, L., Felici, L., Ferraioli, V., Forbici, F., Garbuglia, A. R., Giombini, E., Gruber, C. E. M., Khouri, D., Lalle, E., Leone, B., Mazzarelli, A., Messina, F., Minosse, C., Montaldo, C., Neri, S., Nisii, C., Petrivelli, E., Petroni, F., Petruccioli, E., Pisciotta, M., Pizzi, D., Prota, G., Rozera, G., Rueca, M., Sabatini, R., Sarti, S., Sberna, G., Sciamanna, R., Selleri, M., Selvaggi, C., Stellitano, C., Toffoletti, A., Truffa, S., Turchi, F., Valli, M. B., Venditti, C., Vincenti, D., Vulcano, A., Zambelli, E., Bevilacqua, N., Bordoni, V., D'Abramo, A., Lepore, L., Mariano, A., Palazzolo, C., Lorenzini, P., Notari, S., Sacchi, A., Scorzolini, L., Bettini, A., Francalancia, M., Specchiarello, E., Federica, M., Gaetano, D., Luigi, F., Barbara, G., Roberto, I., Giovanni, M., Mirco, M., and Rachele, S.
Subjects: 0301 basic medicine, Male, lcsh:QR1-502, serology, Antibodies, Viral, lcsh:Microbiology, Serology, protective immunity, 0302 clinical medicine, Medicine, 030212 general & internal medicine, Neutralizing antibody, biology, Middle Aged, 3. Good health, Algorithm, Titer, Infectious Diseases, Female, Neutralization Test, Algorithms, Human, Adult, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Protective immunity, Article, Virus, COVID-19 Serological Testing, 03 medical and health sciences, Neutralization Tests, Immunity, Virology, Neutralizing antibodie, Humans, neutralizing antibodies, Kinetic, Receiver operating characteristic, business.industry, SARS-CoV-2, COVID-19, Gold standard (test), Antibodies, Neutralizing, Kinetics, 030104 developmental biology, ROC Curve, Immunoglobulin G, Immunology, biology.protein, business
Abstract: SARS-CoV-2 serum neutralization assay represents the gold standard for assessing antibody-mediated protection in naturally infected and vaccinated individuals. In the present study, 662 serum samples collected from February 2020 to January 2021 from acute and convalescent COVID-19 patients were tested to determine neutralizing antibody (NAb) titers using a microneutralization test (MNT) for live SARS-CoV-2. Moreover, anti-SARS-CoV-2 IgG, IgA, and IgM directed against different viral antigens were measured by high-throughput automated platforms. We observed higher levels of NAbs in elderly (&gt, 60 years old) individuals and in patients presenting acute respiratory distress syndrome. SARS-CoV-2 NAbs develop as soon as five days from symptom onset and, despite a decline after the second month, persist for over 11 months, showing variable dynamics. Through correlation and receiver operating characteristic (ROC) curve analysis, we set up a testing algorithm, suitable for the laboratory workload, by establishing an optimal cutoff value of anti-SARS-CoV-2 IgG for convalescent plasma donors to exclude from MNT samples foreseen to have low/negative NAb titers and ineligible for plasma donation. Overall, MNT, although cumbersome and not suitable for routine testing of large sample sizes, remains the reference tool for the assessment of antibody-mediated immunity after SARS-CoV-2 infection. Smart testing algorithms may optimize the laboratory workflow to monitor antibody-mediated protection in COVID-19 patients, plasma donors, and vaccinated individuals.
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27. Duration of viral shedding in hospitalized patients infected with pandemic H1N1

Author: Petrosillo Nicola, Ippolito Giuseppe, Ferraro Federica, Valli Maria B, Bordi Licia, Lalle Eleonora, Selleri Marina, Meschi Silvia, Lauria Francesco N, and Capobianchi Maria R
Subjects: Infectious and parasitic diseases, RC109-216
Abstract: Abstract Background The first influenza pandemic of the 21th century was ignited by a new strain of influenza A virus (A/H1N1pdm). Specific patient groups, including those with comorbidities, pregnant women, young children, older and immunocompromised patients, are at increased risk for serious influenza-related disease. This study was aimed at investigating the influence of clinical presentation, antiviral treatment and possible drug resistance-associated mutations, on the extent and duration of viral shedding in patients infected with A/H1N1pdm. Methods An observational study was performed, based on retrospective review of clinical and laboratory records of patients who were hospitalized for A/H1N1pdm infection at the National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy, between April 24 and December 31, 2009. Among 119 hospitalized patients, 39 were selected for a post hoc analysis, based on the availability of serial nasopharyngeal swabs samples and related information. Results Eleven out of the 39 study patients (28.2%) presented with pneumonia; 29 (74.4%) received antiviral treatment. Patients with pneumonia were significantly older than patients without pneumonia. The mean values of viral RNA concentration were not significantly increased in patients with pneumonia, but a significant increase in the duration of viral shedding was observed as compared to patients without pneumonia. In patients receiving antivirals, the viral RNA concentration was significantly reduced in comparison to untreated patients at days 4-5 after symptom onset, while the overall duration of viral shedding was only marginally affected. A significant correlation between duration of viral shedding and time elapsed between symptom onset and therapy start was observed, with a significant reduction of days of viral shedding when therapy was initiated within 2 days of symptoms appearance. No known drug resistance mutations were detected in patients with prolonged viral shedding. Conclusions Our results show that severe respiratory illness is associated with delayed virus clearance in patients with A/H1N1pdm infection. Antivirals caused an early reduction of viral load, but only marginally affected the overall duration of shedding. Prolonged shedding was not associated with the emergence of strains carrying known drug-resistance mutations.
Published: 2011
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28. Characterization of the patterns of drug-resistance mutations in newly diagnosed HIV-1 infected patients naïve to the antiretroviral drugs

Author: Elia Paola, Giuliani Massimo, Bardacci Stefano, Selleri Marina, Ceccherini-Silberstein Francesca, Ciccozzi Massimo, D'Arrigo Roberta, Gori Caterina, Svicher Valentina, Alteri Claudia, Scognamiglio Paola, Balzano Roberta, Orchi Nicoletta, Girardi Enrico, and Perno Carlo
Subjects: Infectious and parasitic diseases, RC109-216
Abstract: Abstract Background The transmission of HIV-1 drug-resistant strains in drug naive patients may seriously compromise the efficacy of a first-line antiretroviral treatment. To better define this problem, a study in a cohort of newly diagnosed HIV-1 infected individuals has been conducted. This study is aimed to assess the prevalence and the patterns of the mutations recently associated with transmitted drug resistance in the reverse transcriptase (RT) and in protease (PR) of HIV-1. Methods Prevalence of transmitted drug resistant strains is determined in 255 newly diagnosed HIV-1 infected patients enrolled in different counselling and testing (CT) centres in Central Italy; the Avidity Index (AI) on the first available serum sample is also used to estimate time since infection. Logistic regression models are used to determine factors associated with infection by drug resistant HIV-1 strains. Results The prevalence of HIV-1 strains with at least one major drug resistance mutation is 5.9% (15/255); moreover, 3.9% (10/255) of patients is infected with HIV nucleoside reverse transcriptase inhibitor (NRTI)-resistant viruses, 3.5% (9/255) with HIV non-NRTI-resistant viruses and 0.4% (1/255) with HIV protease inhibitor (PI)-resistant viruses. Most importantly, almost half (60.0%) of patients carries HIV-1 resistant strains with more than one major drug resistance mutation. In addition, patients who had acquired HIV through homosexual intercourses are more likely to harbour a virus with at least one primary resistance mutation (OR 7.7; 95% CI: 1.7–35.0, P = 0.008). Conclusion The prevalence of drug resistant HIV-1 strains among newly diagnosed individuals in Central Italy is consistent with the data from other European countries. Nevertheless, the presence of drug-resistance HIV-1 mutations in complex patterns highlights an additional potential risk for public health and strongly supports the extension of wide genotyping to newly diagnosed HIV-1 infected patients.
Published: 2009
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29. Dagli appunti di Schiff ai primi passi del sistema periodico nella scuola italiana

Author: TADDIA, MARCO, S. Selleri, M. Fontani, and Taddia, Marco
Subjects: Ugo Schiff, Centenario Schiffiano, Sistema Periodico, Mendeleev
Published: 2017

30. Evaluation of the effects of Human leukocyte INF-alpha on the immune response to the HBV vaccine in healthy unvaccinated individuals

Author: Paola Chionne, Francesca Urbani, Elisabeth A. Haygreen, Enrica Montefiore, Maria Rapicetta, Maria Grimaldi, Maria Rosaria Capobianchi, Imerio Capone, Ernesto Palazzini, Elisabeth Taylor, Persephone Borrow, Paola Rizza, Maria Elena Tosti, A. Scuteri, Marzia Margotti, Pietro Andreone, Filippo Belardelli, Carmela Cursaro, Concetta Castilletti, Giuseppe Claudio Viscomi, Marina Selleri, David F. Tough, Angela Candido, Rizza P, Capone I, Urbani F, Montefiore E, Rapicetta M, Chionne P, Candido A, Tosti ME, Grimaldi M, Palazzini E, Viscomi G, Cursaro C, Margotti M, Scuteri A, Andreone P, Taylor E, Haygreen EA, Tough DF, Borrow P, Selleri M, Castilletti C, Capobianchi M, and Belardelli F.
Subjects: Adult, CD4-Positive T-Lymphocytes, Male, Adolescent, Adjuvant, Interferon, Vaccine, medicine.medical_treatment, Enzyme-Linked Immunosorbent Assay, CD8-Positive T-Lymphocytes, medicine.disease_cause, Peripheral blood mononuclear cell, Interferon-gamma, Immune system, Adjuvants, Immunologic, Immunity, medicine, Humans, Hepatitis B Vaccines, Hepatitis B Antibodies, Antigen-presenting cell, Aged, Hepatitis B virus, General Veterinary, General Immunology and Microbiology, business.industry, Public Health, Environmental and Occupational Health, Interferon-alpha, Dendritic cell, Middle Aged, Flow Cytometry, Virology, Lymphocyte Subsets, Infectious Diseases, Cytokine, Immunoglobulin G, Immunology, Leukocytes, Mononuclear, Molecular Medicine, Female, business
Abstract: HBV vaccine needs 3 injections over 6 months to induce immunity. Thus, the use of adjuvants capable of inducing earlier immune protection would be highly desirable. Most adjuvants may act by inducing cytokines, and among them, type I interferons (IFNs), deserve a special attention in view of the potent immunomostimulatory activity observed in mouse models and on dendritic cell functions. The aim of the present trial was to evaluate the effects of IFN-alpha administered as an adjuvant of HBV vaccine in healthy unvaccinated individuals. No significant enhancing effect on the antibody response was observed, in spite of an early and transient upregulation of costimulatory molecule expression on peripheral blood mononuclear cells, which may be suggestive of an IFN-mediated activation of antigen presenting cells. We conclude that, under the conditions used in this trial, natural IFN-alpha does not act as an adjuvant of the HBV vaccine in healthy unvaccinated individuals.
Published: 2008

31. Clinical impact of medication review and deprescribing in older inpatients: A systematic review and meta-analysis.

Author: Carollo M, Crisafulli S, Vitturi G, Besco M, Hinek D, Sartorio A, Tanara V, Spadacini G, Selleri M, Zanconato V, Fava C, Minuz P, Zamboni M, and Trifirò G
Subjects: Humans, Aged, Hospitalization, Potentially Inappropriate Medication List, Inpatients, Drug-Related Side Effects and Adverse Reactions prevention & control, Drug Interactions, Aged, 80 and over, Prospective Studies, Patient Readmission statistics & numerical data, Deprescriptions, Polypharmacy, Inappropriate Prescribing prevention & control
Abstract: Background: Polypharmacy is a primary risk factor for the prescription of potentially inappropriate medications (PIMs), drug-drug interactions (DDIs), and ultimately, adverse drug reactions (ADRs). Medication review and deprescribing represent effective strategies to simplify therapeutic regimens, minimize risks, and reduce PIM prescriptions. This systematic review and meta-analysis of experimental and observational studies aimed to evaluate the impact of different medication review and deprescribing interventions in hospitalized older patients., Methods: Experimental and observational prospective cohort studies evaluating the clinical effects of medication review and deprescribing strategies in older hospitalized patients were searched in the bibliographic databases, PubMed, Embase, and Scopus, from inception until January 8, 2024. A narrative synthesis of the results was provided, along with a meta-analysis of dichotomous data (i.e., re-hospitalizations and mortality)., Results: Overall, 21 randomized controlled trials, 7 non-randomized interventional studies, and 2 prospective cohort studies were included in the systematic review. Of these, 14 (46.7%) assessed medication appropriateness as the primary outcome, while the remaining evaluated clinical outcomes (e.g., length of hospital stay, hospital readmissions, emergency department visits, and incidence of ADRs) and/or quality of life. The meta-analysis revealed a slight but statistically significant 8% reduction in hospital readmissions (HR: 0.92; 95% CI: 0.85-0.99) following medication review and deprescribing, but no significant impact on mortality (HR: 0.98; 95% CI: 0.96-1.00). Of the 30 included studies, 21 were considered at high risk of bias, mostly due to potential deviations from intended interventions and randomization processes. The remaining nine studies had "some concerns" (eight studies) or were considered at "low" risk of bias (one study)., Conclusion: Medication review and deprescribing are associated with potential benefits in reducing hospital readmission rates among hospitalized older patients, particularly through the reduction of PIM prescriptions. The integration of thorough medication review and deprescribing protocols in hospital settings may improve post-discharge outcomes and reduce overall healthcare costs., (© 2024 The Author(s). Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)
Published: 2024
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32. Agreement of Different Drug-Drug Interaction Checkers for Proton Pump Inhibitors.

Author: Carollo M, Crisafulli S, Selleri M, Piccoli L, L'Abbate L, and Trifirò G
Subjects: Humans, Cross-Sectional Studies, Rabeprazole pharmacology, Lansoprazole, Omeprazole, Esomeprazole, Pantoprazole, Proton Pump Inhibitors, Drug Interactions
Abstract: Importance: Proton pump inhibitors (PPIs) are a widely prescribed class of drugs, potentially interacting with a large number of medicines, especially among older patients with multimorbidity and polypharmacy. Beyond summary of product characteristics (SPCs), interaction checkers (ICs) are routinely used tools to help clinicians in medication review interventions., Objective: To assess the consistency of information on drugs potentially interacting with PPIs as reported in their SPCs and different ICs., Design, Setting, and Participants: This cross-sectional study was conducted using data from SPCs for 5 PPIs (omeprazole, esomeprazole, lansoprazole, pantoprazole, and rabeprazole) and 5 ICs (ie, INTERCheck WEB, Micromedex, Lexicomp, Epocrates, and drugs.com). Information from the SPCs and the ICs were extracted between July 15 and 30, 2023., Main Outcomes and Measures: The main outcome was the level of agreement among SPCs and the 5 ICs in identifying drugs potentially interacting with PPIs and attributing drug-drug interaction (DDI) severity categories. The level of agreement was computed using Gwet AC1 statistic on the 5 ICs and by comparing 4-sets and 2-sets of ICs. As a sensitivity analysis, the level of agreement in listing PPI-related DDIs was evaluated using Cohen κ and Fleiss κ coefficients., Results: Considering SPCs and the 5 ICs, a total of 518 potentially interacting drugs with omeprazole were reported, 455 for esomeprazole, 433 for lansoprazole, 421 for pantoprazole, and 405 for rabeprazole. As compared with the ICs, the SPCs reported a much smaller number of drugs potentially interacting with PPIs, with proportions ranging from 2.7% (11 potentially interacting drugs) for rabeprazole to 7.6% (33 potentially interacting drugs) for lansoprazole of the total identified drugs at risk of interaction with a PPI. The overall level of agreement among the 5 ICs for identifying potential interactions was poor (from 0.23 [95% CI, 0.21-0.25] for omeprazole to 0.27 [95% CI, 0.24-0.29] for pantoprazole and 0.27 [95% CI, 0.25-0.29] for rabeprazole). Similarly, the level of agreement was low in 4-set and 2-set analyses as well as when restricting the analysis to the potential DDIs identified as severe (range, 0.30-0.32)., Conclusions and Relevance: This cross-sectional study found significant disagreement among different ICs and SPCs, highlighting the need to focus on standardizing DDI databases. Therefore, to ensure evaluation and prevention of clinically relevant DDIs, it is recommended to revise multiple ICs and consult with specialists, such as clinical pharmacologists, particularly for patients with complex medical conditions.
Published: 2024
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33. Screening of Klebsiella pneumoniae subsp. pneumoniae Strains with Multi-Drug Resistance and Virulence Profiles Isolated from an Italian Hospital between 2020 and 2023.

Author: Dimartino V, Venditti C, Messina F, D'Arezzo S, Selleri M, Butera O, Nisii C, Marani A, Arcangeli A, Gaziano R, Cosio T, Scanzano P, and Fontana C
Abstract: Klebsiella pneumoniae strains that are resistant to multiple drugs (KPMDRs), which are often acquired in hospital settings and lead to healthcare-associated infections, pose a serious public health threat, as does hypervirulent K. pneumoniae (hvKp), which can also cause serious infections in otherwise healthy individuals. The widespread and often unnecessary use of antibiotics seen during the recent COVID-19 pandemic has exacerbated the challenges posed by antibiotic resistance in clinical settings. There is growing concern that hypervirulent (hvKp) strains may acquire genes that confer antimicrobial resistance, thus combining an MDR profile with their increased ability to spread to multiple body sites, causing difficult-to-treat infections. This study aimed to compare resistance and virulence profiles in KPC-3-producing K. pneumoniae isolates collected over four years (2020-2023). A genome-based surveillance of all MDR CRE- K. pneumoniae was used to identify genetic differences and to characterize the virulence and resistance profiles. Our results provide a picture of the evolution of resistance and virulence genes and contribute to avoiding the possible spread of isolates with characteristics of multi-drug resistance and increased virulence, which are thought to be one of the main global challenges to public health, within our hospital.
Published: 2024
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34. A Cholera Case Imported from Bangladesh to Italy: Clinico-Epidemiological Management and Molecular Characterization in a Non-Endemic Country.

Author: Russini V, Giancola ML, Brunetti G, Calbi C, Anzivino E, Nisii C, Scaramella L, Dionisi AM, Faraglia F, Selleri M, Villa L, Lovari S, De Marchis ML, Bossù T, Vairo F, Pagnanelli A, and Nicastri E
Abstract: Despite the number of cholera outbreaks reported worldwide, only a few cases are recorded among returning European travellers. We describe the case of a 41-year-old male, returning to Italy after a stay in Bangladesh, his origin country, who presented with watery diarrhoea. Vibrio cholerae and norovirus were detected in the patient's stools via multiplex PCR methods. Direct microscopy, Gram staining, culture and antibiotic susceptibility tests were performed. The isolates were tested using end-point PCR for the detection of potentially enteropathogenic V. cholera . Serotype and cholera toxins identification were carried out. Whole genome sequencing and bioinformatics analysis were performed, and antimicrobial resistance genes identified. A phylogenetic tree with the most similar genomes of databases previously described was built. Sample of the food brought back by the patient were also collected and analysed. The patient was diagnosed with V. cholerae O1, serotype Inaba, norovirus and SARS-CoV-2 concomitant infection. The isolated V. cholerae strain was found to belong to ST69, encoding for cholera toxin, ctxB7 type and was phylogenetically related to the 2018 outbreak in Dhaka, Bangladesh. Adopting a multidisciplinary approach in a cholera non-endemic country ensured rapid and accurate diagnosis, timely clinical management, and epidemiological investigation at national and international level.
Published: 2023
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35. Incidence of bacterial and fungal bloodstream infections in COVID-19 patients in intensive care: An alarming "collateral effect".

Author: Cataldo MA, Tetaj N, Selleri M, Marchioni L, Capone A, Caraffa E, Caro AD, and Petrosillo N
Subjects: Aged, Bacteremia blood, Bacteremia virology, Bacteria isolation & purification, COVID-19 blood, COVID-19 epidemiology, Cohort Studies, Coinfection blood, Coinfection microbiology, Critical Care statistics & numerical data, Female, Fungemia blood, Fungemia virology, Fungi isolation & purification, Humans, Incidence, Italy epidemiology, Male, Middle Aged, Mortality, Retrospective Studies, SARS-CoV-2 isolation & purification, Bacteremia epidemiology, COVID-19 microbiology, Fungemia epidemiology
Published: 2020
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36. Analysis of hepatitis B virus-mixed genotype infection by ultra deep pyrosequencing in Sudanese patients, 2015-2016.

Author: Enan KA, Minosse C, El Hussein ARM, Selleri M, Giombini E, Capobianchi MR, Elkhidir IM, Mustafa MO, Khair OM, Hassan DA, and Garbuglia AR
Subjects: Amino Acid Sequence, Coinfection virology, DNA, Viral genetics, Genotype, Humans, Mutation, Phylogeny, Sequence Analysis, DNA, Sudan, Hepatitis B virology, Hepatitis B virus genetics, High-Throughput Nucleotide Sequencing
Abstract: Purpose: The frequency of detection of HBV co-infection with multiple HBV genotypes is influenced by the detection method; usually co-infections are detected by multiplex PCR or hybridization assays, and are rarely confirmed by sequencing and conventional cloning. The objective of this study was to confirm by ultra-deep pyrosequencing (UDPS) mixed HBV infections, previously detected by multiplex-nested PCR., Methods: Sixteen samples from HBV co-infected Sudanese patients detected by multiplex-nested PCR, were amplified targeting the P/S region and sequenced by UDPS., Results: The only genotypes identified using UDPS were D and E, while A, B, C and F genotypes, previously detected by multiplex-nested PCR, were not detected. Specifically, 10 samples were shown to be mono-infected (D or E); in 3 out of 10 mono-infected D patients, a subtype combination was observed: D1 + D7 in 2 cases and D2 + D6 in 1 case. The remaining 6 subjects were D + E co-infected (harboring different mixtures of D subtypes)., Conclusions: Overall, UDPS is more effective than multiplex-nested PCR for identifying multiple HBV genotypes and subtypes infections.
Published: 2019
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37. Epidemiological investigation of an Acinetobacter baumannii outbreak using core genome multilocus sequence typing.

Author: Venditti C, Vulcano A, D'Arezzo S, Gruber CEM, Selleri M, Antonini M, Lanini S, Marani A, Puro V, Nisii C, and Di Caro A
Subjects: Acinetobacter baumannii drug effects, Anti-Bacterial Agents pharmacology, Bacterial Proteins genetics, Bacterial Typing Techniques methods, Carbapenem-Resistant Enterobacteriaceae genetics, Carbapenems, Humans, Intensive Care Units, Italy, Microbial Sensitivity Tests, Phylogeny, Polymerase Chain Reaction, Whole Genome Sequencing, beta-Lactamases genetics, Acinetobacter Infections epidemiology, Acinetobacter baumannii genetics, Acinetobacter baumannii isolation & purification, Disease Outbreaks, Molecular Epidemiology, Multilocus Sequence Typing methods
Abstract: Objectives: Carbapenem-resistant Acinetobacter baumannii (CRAB) is a serious nosocomial pathogen that causes a variety of serious, often life-threatening, infections and outbreaks. This study aimed to investigate the molecular epidemiology of clinical CRAB isolates from an outbreak that occurred in the intensive care unit (ICU) of an Italian hospital., Methods: From December 2016 to April 2017, 13 CRAB isolates were collected from seven patients treated in the ICU at 'L. Spallanzani' Hospital (Rome, Italy). Typing was performed by repetitive extragenic palindromic PCR (rep-PCR) using a DiversiLab ® system. Whole-genome sequencing (WGS) data were used for in silico analysis of traditional multilocus sequence typing (MLST) results, to identify resistance genes and for core genome MLST (cgMLST) analysis. Epidemiological data were obtained from hospital records., Results: All isolates showed a carbapenem-resistant profile and carried the bla OXA-23 carbapenemase gene. Typing performed by rep-PCR and MLST showed that the isolates clustered into one group, whilst the cgMLST approach, which uses 2390 gene targets to characterise the gene-by-gene allelic profile, highlighted the presence of two cluster types. These results allowed us to identify two patients who were likely to be the source of two separate transmission chains., Conclusion: These results show that WGS by cgMLST is a valuable tool, better suited for prompt epidemiological investigations than traditional typing methods because of its higher discriminatory ability in determining clonal relatedness., (Copyright © 2018 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.)
Published: 2019
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38. Whole Genome Characterization of Orthopoxvirus (OPV) Abatino, a Zoonotic Virus Representing a Putative Novel Clade of Old World Orthopoxviruses.

Author: Gruber CEM, Giombini E, Selleri M, Tausch SH, Andrusch A, Tyshaieva A, Cardeti G, Lorenzetti R, De Marco L, Carletti F, Nitsche A, Capobianchi MR, Ippolito G, Autorino GL, and Castilletti C
Subjects: Animals, DNA, Viral genetics, Genes, Viral genetics, Sequence Analysis, DNA, Sequence Homology, Nucleic Acid, Cercopithecidae virology, Genome, Viral genetics, Orthopoxvirus classification, Orthopoxvirus genetics, Phylogeny
Abstract: Orthopoxviruses (OPVs) are diffused over the complete Eurasian continent, but previously described strains are mostly from northern Europe, and few infections have been reported from Italy. Here we present the extended genomic characterization of OPV Abatino, a novel OPV isolated in Italy from an infected Tonkean macaque, with zoonotic potential. Phylogenetic analysis based on 102 conserved OPV genes (core gene set) showed that OPV Abatino is most closely related to the Ectromelia virus species (ECTV), although placed on a separate branch of the phylogenetic tree, bringing substantial support to the hypothesis that this strain may be part of a novel OPV clade. Extending the analysis to the entire set of genes (coding sequences, CDS) further substantiated this hypothesis. In fact the genome of OPV Abatino included more CDS than ECTV; most of the extra genes (mainly located in the terminal genome regions), showed the highest similarity with cowpox virus (CPXV); however vaccinia virus (VACV) and monkeypox virus (MPXV) were the closest OPV for certain CDS. These findings suggest that OPV Abatino could be the result of complex evolutionary events, diverging from any other previously described OPV, and may indicate that previously reported cases in Italy could represent the tip of the iceberg yet to be explored.
Published: 2018
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39. Fatal Outbreak in Tonkean Macaques Caused by Possibly Novel Orthopoxvirus, Italy, January 2015 1 .

Author: Cardeti G, Gruber CEM, Eleni C, Carletti F, Castilletti C, Manna G, Rosone F, Giombini E, Selleri M, Lapa D, Puro V, Di Caro A, Lorenzetti R, Scicluna MT, Grifoni G, Rizzoli A, Tagliapietra V, De Marco L, Capobianchi MR, and Autorino GL
Subjects: Animals, Antibodies, Viral blood, Housing, Animal, Immunity, Humoral drug effects, Immunoglobulin G blood, Italy epidemiology, Macaca, Male, Monkey Diseases immunology, Monkey Diseases mortality, Monkey Diseases prevention & control, Orthopoxvirus classification, Orthopoxvirus isolation & purification, Orthopoxvirus pathogenicity, Poxviridae Infections mortality, Poxviridae Infections prevention & control, Rats, Rodentia virology, Skin pathology, Skin virology, Survival Analysis, Vaccination, Viral Vaccines administration & dosage, Disease Outbreaks, Monkey Diseases epidemiology, Orthopoxvirus genetics, Phylogeny, Poxviridae Infections epidemiology, Poxviridae Infections veterinary
Abstract: In January 2015, during a 3-week period, 12 captive Tonkean macacques at a sanctuary in Italy died. An orthopoxvirus infection was suspected because of negative-staining electron microscopy results. The diagnosis was confirmed by histology, virus isolation, and molecular analysis performed on different organs from all animals. An epidemiologic investigation was unable to define the infection source in the surrounding area. Trapped rodents were negative by virologic testing, but specific IgG was detected in 27.27% of small rodents and 14.28% of rats. An attenuated live vaccine was administered to the susceptible monkey population, and no adverse reactions were observed; a detectable humoral immune response was induced in most of the vaccinated animals. We performed molecular characterization of the orthopoxvirus isolate by next-generation sequencing. According to the phylogenetic analysis of the 9 conserved genes, the virus could be part of a novel clade, lying between cowpox and ectromelia viruses.
Published: 2017
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40. In-Depth Analysis of HA and NS1 Genes in A(H1N1)pdm09 Infected Patients.

Author: Caglioti C, Selleri M, Rozera G, Giombini E, Zaccaro P, Valli MB, and Capobianchi MR
Subjects: Adolescent, Adult, Aged, Female, Genes, Viral, Genetic Variation, Humans, Influenza A Virus, H1N1 Subtype classification, Male, Middle Aged, RNA, Viral, Sequence Analysis, RNA, Young Adult, Hemagglutinin Glycoproteins, Influenza Virus genetics, Influenza A Virus, H1N1 Subtype genetics, Influenza, Human virology, Viral Nonstructural Proteins genetics
Abstract: In March/April 2009, a new pandemic influenza A virus (A(H1N1)pdm09) emerged and spread rapidly via human-to-human transmission, giving rise to the first pandemic of the 21th century. Influenza virus may be present in the infected host as a mixture of variants, referred to as quasi-species, on which natural and immune-driven selection operates. Since hemagglutinin (HA) and non-structural 1 (NS1) proteins are relevant in respect of adaptive and innate immune responses, the present study was aimed at establishing the intra-host genetic heterogeneity of HA and NS1 genes, applying ultra-deep pyrosequencing (UDPS) to nasopharyngeal swabs (NPS) from patients with confirmed influenza A(H1N1)pdm09 infection. The intra-patient nucleotide diversity of HA was significantly higher than that of NS1 (median (IQR): 37.9 (32.8-42.3) X 10(-4) vs 30.6 (27.4-33.6) X 10(-4) substitutions/site, p = 0.024); no significant correlation for nucleotide diversity of NS1 and HA was observed (r = 0.319, p = 0.29). Furthermore, a strong inverse correlation between nucleotide diversity of NS1 and viral load was observed (r = - 0.74, p = 0.004). For both HA and NS1, the variants appeared scattered along the genes, thus indicating no privileged mutation site. Known polymorphisms, S203T (HA) and I123V (NS1), were observed as dominant variants (>98%) in almost all patients; three HA and two NS1 further variants were observed at frequency >40%; a number of additional variants were detected at frequency <6% (minority variants), of which three HA and four NS1 variants were novel. In few patients multiple variants were observed at HA residues 203 and 222. According to the FLUSURVER tool, some of these variants may affect immune recognition and host range; however, these inferences are based on H5N1, and their extension to A(H1N1)pdm09 requires caution. More studies are necessary to address the significance of the composite nature of influenza virus quasi-species within infected patients.
Published: 2016
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41. Role of HIV-1 matrix protein p17 variants in lymphoma pathogenesis.

Author: Dolcetti R, Giagulli C, He W, Selleri M, Caccuri F, Eyzaguirre LM, Mazzuca P, Corbellini S, Campilongo F, Marsico S, Giombini E, Muraro E, Rozera G, De Paoli P, Carbone A, Capobianchi MR, Ippolito G, Fiorentini S, Blattner WA, Lu W, Gallo RC, and Caruso A
Subjects: Adult, B-Lymphocytes metabolism, B-Lymphocytes pathology, Cell Line, Tumor, Female, HIV Antigens genetics, HIV Infections genetics, HIV Infections pathology, HIV-1 genetics, Humans, Lymphoma, B-Cell genetics, Male, Middle Aged, Mutagenesis, Insertional, Proto-Oncogene Proteins c-akt genetics, Proto-Oncogene Proteins c-akt metabolism, Signal Transduction genetics, gag Gene Products, Human Immunodeficiency Virus genetics, Cell Transformation, Viral, HIV Antigens metabolism, HIV Infections metabolism, HIV-1 metabolism, Lymphoma, B-Cell metabolism, gag Gene Products, Human Immunodeficiency Virus metabolism
Abstract: Although in decline after successful anti-HIV therapy, B-cell lymphomas are still elevated in HIV-1-seropositive (HIV+) persons, and the mechanisms are obscure. The HIV-1 matrix protein p17 persists in germinal centers long after HIV-1 drug suppression, and some p17 variants (vp17s) activate Akt signaling and promote growth of transformed B cells. Here we show that vp17s derived from four of five non-Hodgkin lymphoma (NHL) tissues from HIV+ subjects display potent B-cell growth-promoting activity. They are characterized by amino acid insertions at position 117-118 (Ala-Ala) or 125-126 (Gly-Asn or Gly-Gln-Ala-Asn-Gln-Asn) among some other mutations throughout the sequence. Identical dominant vp17s are found in both tumor and plasma. Three of seven plasma samples from an independent set of NHL cases manifested multiple Ala insertions at position 117-118, and one with the Ala-Ala profile also promoted B-cell growth and activated Akt signaling. Ultradeep pyrosequencing showed that vp17s with C-terminal insertions are more frequently detected in plasma of HIV+ subjects with than without NHL. Insertion of Ala-Ala at position 117-118 into reference p17 (refp17) was sufficient to confer B-cell growth-promoting activity. In contrast, refp17 bearing the Gly-Asn insertion at position 125-126 did not, suggesting that mutations not restricted to the C terminus can also account for this activity. Biophysical analysis revealed that the Ala-Ala insertion mutant is destabilized compared with refp17, whereas the Gly-Asn form is stabilized. This finding provides an avenue for further exploration of structure function relationships and new treatment strategies in combating HIV-1-related NHL.
Published: 2015
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42. HCV NS3 quasispecies in liver and plasma and dynamics of telaprevir-resistant variants in breakthrough patients assessed by UDPS: A case study.

Author: Bartolini B, Selleri M, Garbuglia AR, Giombini E, Taibi C, Lionetti R, D'Offizi G, and Capobianchi MR
Subjects: Antiviral Agents pharmacology, Genetic Variation, Hepacivirus drug effects, Hepacivirus isolation & purification, Hepatitis C, Chronic drug therapy, High-Throughput Nucleotide Sequencing, Humans, Liver virology, Longitudinal Studies, Oligopeptides pharmacology, Plasma virology, Viral Load, Antiviral Agents therapeutic use, Drug Resistance, Viral, Genotype, Hepacivirus genetics, Hepatitis C, Chronic virology, Oligopeptides therapeutic use, Viral Nonstructural Proteins genetics
Abstract: Background: The impact of pre-existing variants in hepatitis C virus (HCV) quasispecies, carrying resistance-associated mutations (RAMs), on the outcome of treatment with direct acting antiviral agents (DAA) is debated and it is complicated by the lack of knowledge of quasispecies distribution between the viral reservoir (liver) and the circulating compartment., Objective: To evaluate NS3 protease heterogeneity and presence of RAMs on baseline plasma and liver biopsy samples. Plasma dynamics were also analyzed during therapy and after its suspension. Study design Ultra-deep pyrosequencing (UDPS) was performed in two HCV genotype 1a patients who received telaprevir (TVR)-based therapy and developed treatment failure due to TVR-resistance., Results: In both patients the baseline diversity of NS3 quasispecies in plasma was higher than in liver (183.6×10(-4) vs 47.8×10(-4) and 246.0×10(-4) vs 55.0×10(-4) nt substitution/site, respectively, p<0.0001), but phylogenetic trees did not evidence compartmentalization between the two compartments. At baseline RAMs (i.e. V36A, T54A) were detected very low levels (range: 0.31-0.52%) in both specimen types. However, phylogenetic analyses revealed that the viral variants carrying these mutations at baseline were different from those that became fixed at breakthrough, when combined V36M+R155K, conferring high-level resistance to TVR, were observed. The frequency of resistance-associated variants declined after withdrawal of drug selective pressure., Conclusions: UDPS allowed extensive evaluation of quasispecies compartmentalization and of their dynamics after withdrawal of TVR. Plasma and liver NS3 quasispecies, including low level RAMs, do not show significant difference., (Copyright © 2015 Elsevier B.V. All rights reserved.)
Published: 2015
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43. Near full length hepatitis C virus genome reconstruction by next generation sequencing based on genotype-independent amplification.

Author: Bartolini B, Giombini E, Abbate I, Selleri M, Rozera G, Biagini T, Visco-Comandini U, Taibi C, and Capobianchi MR
Subjects: Aged, Aged, 80 and over, DNA, Viral analysis, Female, Genotype, Humans, Male, Middle Aged, Phylogeny, RNA, Viral isolation & purification, Retrospective Studies, Reverse Transcriptase Polymerase Chain Reaction, Sequence Analysis, DNA, Genome, Viral, Genotyping Techniques methods, Hepacivirus genetics, Hepatitis C virology, High-Throughput Nucleotide Sequencing methods
Abstract: Background: Deep sequencing has a deep impact on the study of rapidly mutating RNA viruses, such as hepatitis C virus, proving to be an invaluable tool for analyzing virus diversity and evolution., Aim: Genotype-independent high-throughput pyrosequencing was used to obtain near full length hepatitis C virus genome sequence reconstruction directly from clinical samples., Methods: Samples from hepatitis C virus infected subjects harbouring different subtypes (1a, 1b, 2c) were analyzed (viral load range: 1.2-20.8 × 10(6)IU/ml). Data were generated with a modified sequence-independent single primer amplification method followed by 454 sequencing., Results: the extent of reconstructed hepatitis C virus genome varied from 79.95% to 99.64%. No correlation between extent of genome reconstruction and either viral load (r=0.4857, p=0.3556) or number of HCV reads (r=0.08571, p=0.9194) was observed., Conclusion: This study describes a protocol for obtaining whole genome sequences from different hepatitis C virus patients with different genotypes in a single sequencing run., (Copyright © 2015 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.)
Published: 2015
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44. Detection of HIV-1 matrix protein p17 quasispecies variants in plasma of chronic HIV-1-infected patients by ultra-deep pyrosequencing.

Author: Giombini E, Dolcetti R, Caccuri F, Selleri M, Rozera G, Abbate I, Bartolini B, Martorelli D, Faè DA, Fiorentini S, Giagulli C, Capobianchi MR, and Caruso A
Subjects: Adult, Female, Genetic Variation, Humans, Male, Middle Aged, RNA, Viral genetics, Sequence Analysis, DNA methods, Young Adult, HIV Antigens genetics, HIV Infections virology, HIV-1 genetics, gag Gene Products, Human Immunodeficiency Virus genetics
Abstract: Background: The HIV-1 matrix protein p17 (p17MA) is a pleiotropic protein that plays a key role in the HIV-1 life cycle. It has been long believed to have a highly conserved primary amino acid sequence and a well-preserved structural integrity to avoid severe fitness consequences. However, recent data revealed that the carboxy (COOH)-terminus of p17MA possesses high levels of predicted intrinsic disorder, which would subtend to at least partially unfolded status of this region. This finding pointed to the need of investigating p17MA heterogeneity., Methods: The degree of intrapatient variations in the p17MA primary sequence was assessed on plasma viral RNA by using ultra-deep pyrosequencing., Results: Data obtained support a complex nature of p17MA quasispecies, with variants present at variable frequency virtually in all patients. Clusters of mutations were scattered along the entire sequence of the viral protein, but they were more frequently detected within the COOH-terminal region of p17MA. Moreover, deletions and insertions also occurred in a restricted area of the COOH-terminal region., Conclusions: On the whole, our data show that the intrapatient level of sequence diversity in the p17MA is much higher than predicted before. Our results pave the way for further studies aimed at unraveling possible correlations between the presence of distinct p17MA variants and peculiar clinical evolutions of HIV-1 disease. The presence of p17MA quasispecies diversity may offer new tools to improve our understanding of the viral adaptation during the natural history of HIV-1 infection.
Published: 2014
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45. Extent of HCV NS3 protease variability and resistance-associated mutations assessed by next generation sequencing in HCV monoinfected and HIV/HCV coinfected patients.

Author: Bartolini B, Giombini E, Zaccaro P, Selleri M, Rozera G, Abbate I, Comandini UV, Ippolito G, Solmone M, and Capobianchi MR
Subjects: Adult, Aged, Drug Resistance, Viral, Female, Genetic Variation, HIV-1 physiology, Hepacivirus classification, Hepacivirus genetics, High-Throughput Nucleotide Sequencing, Humans, Male, Middle Aged, Viral Nonstructural Proteins metabolism, Coinfection virology, HIV Infections virology, Hepacivirus enzymology, Hepatitis C virology, Mutation, Missense, Viral Nonstructural Proteins genetics
Abstract: HCV quasispecies variability represents the background for the selection of mutations and for the development of drug resistance. Natural aminoacid changes in NS3, associated with reduced protease inhibitor susceptibility, have been observed in treatment-naïve patients. Massively parallel sequencing has been used to analyze NS3 quasispecies in patients infected with HCV genotype 1, naive to anti-HCV treatment, with/without HIV-coinfection, to establish the genetic heterogeneity and the presence of amino acid substitutions at positions responsible for drug resistance. Genomes carrying substitutions represented either predominant or minority components of viral quasispecies, and were observed in 85.7% of patients. Multiple substitutions, frequently associated on the same haplotype, were observed in 46.4% of patients. High resistance combinations were not detected, neither on the same genome, nor in the whole quasispecies. Heterogeneity of HCV NS3 was lower in HIV-coinfected as compared to HCV-monoinfected patients, but factors underlying this difference remain to be established. Although the relevance of naturally occurring mutations with respect of resistance development and probability of success of direct acting antivirals is questioned, UDPS may be beneficial to help understanding viral dynamics, providing high resolution view of viral diversity., (Copyright © 2013 Elsevier B.V. All rights reserved.)
Published: 2013
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46. Comparison of two real-time RT-PCR-based systems for the detection and typing of the pandemic influenza A virus, 2009.

Author: Lalle E, Bordi L, Meschi S, Selleri M, Valli MB, Patella E, and Capobianchi MR
Subjects: Centers for Disease Control and Prevention, U.S., Genes, Viral, Humans, Influenza A Virus, H1N1 Subtype genetics, Influenza A Virus, H1N1 Subtype isolation & purification, Influenza, Human epidemiology, Influenza, Human virology, Italy epidemiology, Microbiological Techniques, Pandemics, RNA, Viral genetics, Sensitivity and Specificity, United States, Viral Matrix Proteins genetics, Influenza A Virus, H1N1 Subtype classification, Influenza, Human diagnosis, Reagent Kits, Diagnostic, Reverse Transcriptase Polymerase Chain Reaction methods
Abstract: During the 2009 pandemic the Virology Laboratory of L. Spallanzani, Rome, Italy, adopted a real-time RT-PCR developed by the Centers for Disease Control and Prevention (CDC), Atlanta, Georgia to diagnose pandemic influenza A/H1N1 (H1N1pdm). A new multiplex real-time RT-PCR distributed by Astra Diagnostics, coupled with the extraction system developed and commercialized by Siemens Healthcare Diagnostics (referred to as the RealStar system), was tested for the ability to detect and type influenza A in clinical samples, with particular emphasis on influenza A-positive samples untyped by the CDC method. Seventy-six nasopharyngeal swabs, resulting by the CDC method H1N1pdm (n=7), H3N2 (n=3), and not subtyped (n=66), were re-analysed with the RealStar system. All H3N2 and H1N1pdm-positive samples were correctly identified; among the untyped samples, the RealStar system detected 24/66 (36.4%) H1N1pdm and 1/66 (1.5%) seasonal influenza A. In conclusion, the RealStar system confirmed the results of all the influenza A-positive samples subtyped by the CDC method, and was able to type 37.9% of samples untyped by the CDC method. However, 62.1% of samples, detected as influenza A-positive but not subtyped by the CDC method, were found to be negative by the RealStar system. Further investigation is needed to explain this latter, unexpected, finding., (Copyright © 2011 Elsevier B.V. All rights reserved.)
Published: 2011
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47. Duration of viral shedding in hospitalized patients infected with pandemic H1N1.

Author: Meschi S, Selleri M, Lalle E, Bordi L, Valli MB, Ferraro F, Ippolito G, Petrosillo N, Lauria FN, and Capobianchi MR
Subjects: Adolescent, Adult, Antiviral Agents pharmacology, Antiviral Agents therapeutic use, Female, Hospitalization, Humans, Influenza A Virus, H1N1 Subtype drug effects, Influenza A Virus, H1N1 Subtype genetics, Influenza A Virus, H1N1 Subtype isolation & purification, Influenza, Human drug therapy, Influenza, Human epidemiology, Italy epidemiology, Male, Middle Aged, Molecular Sequence Data, Pandemics, Retrospective Studies, Time Factors, Viral Load, Young Adult, Influenza A Virus, H1N1 Subtype physiology, Influenza, Human virology, Virus Shedding
Abstract: Background: The first influenza pandemic of the 21th century was ignited by a new strain of influenza A virus (A/H1N1pdm). Specific patient groups, including those with comorbidities, pregnant women, young children, older and immunocompromised patients, are at increased risk for serious influenza-related disease. This study was aimed at investigating the influence of clinical presentation, antiviral treatment and possible drug resistance-associated mutations, on the extent and duration of viral shedding in patients infected with A/H1N1pdm., Methods: An observational study was performed, based on retrospective review of clinical and laboratory records of patients who were hospitalized for A/H1N1pdm infection at the National Institute for Infectious Diseases "L. Spallanzani", Rome, Italy, between April 24 and December 31, 2009. Among 119 hospitalized patients, 39 were selected for a post hoc analysis, based on the availability of serial nasopharyngeal swabs samples and related information., Results: Eleven out of the 39 study patients (28.2%) presented with pneumonia; 29 (74.4%) received antiviral treatment. Patients with pneumonia were significantly older than patients without pneumonia. The mean values of viral RNA concentration were not significantly increased in patients with pneumonia, but a significant increase in the duration of viral shedding was observed as compared to patients without pneumonia. In patients receiving antivirals, the viral RNA concentration was significantly reduced in comparison to untreated patients at days 4-5 after symptom onset, while the overall duration of viral shedding was only marginally affected. A significant correlation between duration of viral shedding and time elapsed between symptom onset and therapy start was observed, with a significant reduction of days of viral shedding when therapy was initiated within 2 days of symptoms appearance. No known drug resistance mutations were detected in patients with prolonged viral shedding., Conclusions: Our results show that severe respiratory illness is associated with delayed virus clearance in patients with A/H1N1pdm infection. Antivirals caused an early reduction of viral load, but only marginally affected the overall duration of shedding. Prolonged shedding was not associated with the emergence of strains carrying known drug-resistance mutations.
Published: 2011
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48. Hemagglutinin 222 variants in pandemic (H1N1) 2009 virus.

Author: Valli MB, Selleri M, Meschi S, Zaccaro P, Vincenti D, Lalle E, Capobianchi MR, and Menzo S
Subjects: Amino Acid Substitution, Codon genetics, Humans, Italy epidemiology, Molecular Sequence Data, Mutation genetics, Phylogeny, Genetic Variation, Hemagglutinins, Viral genetics, Influenza A Virus, H1N1 Subtype genetics, Influenza, Human epidemiology, Influenza, Human virology, Pandemics
Published: 2011
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49. Chikungunya virus isolates with/without A226V mutation show different sensitivity to IFN-a, but similar replication kinetics in non human primate cells.

Author: Bordi L, Meschi S, Selleri M, Lalle E, Castilletti C, Carletti F, Chiappini R, Di Caro A, and Capobianchi MR
Subjects: Alphavirus Infections immunology, Animals, Chikungunya virus drug effects, Chikungunya virus pathogenicity, Chikungunya virus physiology, Chlorocebus aethiops, Humans, Interferon Type I genetics, Recombinant Proteins, Vero Cells, Viral Envelope Proteins immunology, Virus Replication genetics, Alphavirus Infections virology, Chikungunya virus genetics, Interferon Type I pharmacology, Mutation, Missense, Viral Envelope Proteins genetics
Abstract: Chikungunya virus (CHIKV) is a mosquito-transmitted alphavirus responsible for the first autochthonous Italian outbreak in 2007. A226V mutation in E1 has been associated with enhanced replication in A. albopictus vector. Possible involvement of this mutation in enhanced infection capability in primate cells and sensitivity to exogenous interferon (IFN)-a was investigated. No significant differences were observed between the two isolates in terms of replication kinetic, virus yield and cytopathic effect (CPE). Interestingly, the A226V-carrying strain was more susceptible to the antiviral action of recombinant IFN-a. The interplay between A226V mutation and innate defence mechanisms needs further investigation.
Published: 2011

50. Frequency of detection of upper respiratory tract viruses in patients tested for pandemic H1N1/09 viral infection.

Author: Nisii C, Meschi S, Selleri M, Bordi L, Castilletti C, Valli MB, Lalle E, Lauria FN, Piselli P, Lanini S, Ippolito G, Di Caro A, and Capobianchi MR
Subjects: Adult, Comorbidity, Hospitalization, Humans, Influenza A Virus, H1N1 Subtype isolation & purification, Middle Aged, Parainfluenza Virus 3, Human isolation & purification, Prevalence, Respiratory Tract Infections pathology, Nasopharynx virology, Respiratory Tract Infections epidemiology, Respiratory Tract Infections virology, Viruses classification, Viruses isolation & purification
Abstract: Molecular testing of 270 consecutive nasopharyngeal swab samples taken in May and June 2009 and 274 samples from patients hospitalized between July and December 2009 showed similar findings of respiratory viruses, with influenza A pandemic virus H1N1/09 being the most represented, followed by human parainfluenza virus type 3 and rhinoviruses. Statistical analyses suggested virus cocirculation in the absence of viral interference.
Published: 2010
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