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Emanuela Giombini
National Institute for Infectious Diseases, “Lazzaro Spallanzani”–IRCCS, Via Portuense, 292, 00149 Rome, Italy

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Journal article
Published: 06 July 2021 in Viruses
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Complex systems are inherently multilevel and multiscale systems. The infectious disease system is considered a complex system resulting from the interaction between three sub-systems (host, pathogen, and environment) organized into a hierarchical structure, ranging from the cellular to the macro-ecosystem level, with multiscales. Therefore, to describe infectious disease phenomena that change through time and space and at different scales, we built a model framework where infectious disease must be considered the set of biological responses of human hosts to pathogens, with biological pathways shared with other pathologies in an ecological interaction context. In this paper, we aimed to design a framework for building a disease model for COVID-19 based on current literature evidence. The model was set up by identifying the molecular pathophysiology related to the COVID-19 phenotypes, collecting the mechanistic knowledge scattered across scientific literature and bioinformatic databases, and integrating it using a logical/conceptual model systems biology. The model framework building process began from the results of a domain-based literature review regarding a multiomics approach to COVID-19. This evidence allowed us to define a framework of COVID-19 conceptual model and to report all concepts in a multilevel and multiscale structure. The same interdisciplinary working groups that carried out the scoping review were involved. The conclusive result is a conceptual method to design multiscale models of infectious diseases. The methodology, applied in this paper, is a set of partially ordered research and development activities that result in a COVID-19 multiscale model.

ACS Style

Francesco Messina; Chiara Montaldo; Isabella Abbate; Manuela Antonioli; Veronica Bordoni; Giulia Matusali; Alessandra Sacchi; Emanuela Giombini; Gian Fimia; Mauro Piacentini; Maria Capobianchi; Francesco Lauria; Giuseppe Ippolito; on behalf of COVID-19 Scoping Review Working Group. Rationale and Criteria for a COVID-19 Model Framework. Viruses 2021, 13, 1309 .

AMA Style

Francesco Messina, Chiara Montaldo, Isabella Abbate, Manuela Antonioli, Veronica Bordoni, Giulia Matusali, Alessandra Sacchi, Emanuela Giombini, Gian Fimia, Mauro Piacentini, Maria Capobianchi, Francesco Lauria, Giuseppe Ippolito, on behalf of COVID-19 Scoping Review Working Group. Rationale and Criteria for a COVID-19 Model Framework. Viruses. 2021; 13 (7):1309.

Chicago/Turabian Style

Francesco Messina; Chiara Montaldo; Isabella Abbate; Manuela Antonioli; Veronica Bordoni; Giulia Matusali; Alessandra Sacchi; Emanuela Giombini; Gian Fimia; Mauro Piacentini; Maria Capobianchi; Francesco Lauria; Giuseppe Ippolito; on behalf of COVID-19 Scoping Review Working Group. 2021. "Rationale and Criteria for a COVID-19 Model Framework." Viruses 13, no. 7: 1309.

Journal article
Published: 25 January 2021 in Viruses
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Molecular investigation of primary HIV infections (PHI) is crucial to describe current dynamics of HIV transmission. Aim of the study was to investigate HIV transmission clusters (TC) in PHI referred during the years 2013–2020 to the National Institute for Infectious Diseases in Rome (INMI), that is the Lazio regional AIDS reference centre, and factors possibly associated with inclusion in TC. These were identified by phylogenetic analysis, based on population sequencing of pol; a more in depth analysis was performed on TC of B subtype, using ultra-deep sequencing (UDS) of env. Of 270 patients diagnosed with PHI during the study period, 229 were enrolled (median follow-up 168 (IQR 96–232) weeks). Median age: 39 (IQR 32–48) years; 94.8% males, 86.5% Italians, 83.4% MSM, 56.8% carrying HIV-1 subtype B. Of them, 92.6% started early treatment within a median of 4 (IQR 2–7) days after diagnosis; median time to sustained suppression was 20 (IQR 8–32) weeks. Twenty TC (median size 3, range 2–9 individuals), including 68 patients, were identified. A diagnosis prior to 2015 was the unique factor associated with inclusion in a TC. Added value of UDS was the identification of shared quasispecies components in transmission pairs within TC.

ACS Style

Lavinia Fabeni; Gabriella Rozera; Giulia Berno; Emanuela Giombini; Caterina Gori; Nicoletta Orchi; Gabriella De Carli; Silvia Pittalis; Vincenzo Puro; Carmela Pinnetti; Annalisa Mondi; Marta Camici; Maria Plazzi; Andrea Antinori; Maria Capobianchi; Isabella Abbate. Molecular Transmission Dynamics of Primary HIV Infections in Lazio Region, Years 2013–2020. Viruses 2021, 13, 176 .

AMA Style

Lavinia Fabeni, Gabriella Rozera, Giulia Berno, Emanuela Giombini, Caterina Gori, Nicoletta Orchi, Gabriella De Carli, Silvia Pittalis, Vincenzo Puro, Carmela Pinnetti, Annalisa Mondi, Marta Camici, Maria Plazzi, Andrea Antinori, Maria Capobianchi, Isabella Abbate. Molecular Transmission Dynamics of Primary HIV Infections in Lazio Region, Years 2013–2020. Viruses. 2021; 13 (2):176.

Chicago/Turabian Style

Lavinia Fabeni; Gabriella Rozera; Giulia Berno; Emanuela Giombini; Caterina Gori; Nicoletta Orchi; Gabriella De Carli; Silvia Pittalis; Vincenzo Puro; Carmela Pinnetti; Annalisa Mondi; Marta Camici; Maria Plazzi; Andrea Antinori; Maria Capobianchi; Isabella Abbate. 2021. "Molecular Transmission Dynamics of Primary HIV Infections in Lazio Region, Years 2013–2020." Viruses 13, no. 2: 176.

Preprint content
Published: 30 November 2020
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A new SARS-CoV-2 clade (GV) characterized by S substitution A222V, first reported from Spain in March, is rapidly spreading across Europe. To establish the A222V variant involvement in the infection rise in Italy, all GISAID sequences from Italy and those from our Laboratory (Lazio) in the period June-October were analysed. A222V, first recognized in August, represents 11.2% of sequences in this period, reaching 100% of autochthonous sequences in October, supporting increased GV circulation in Italy.

ACS Style

Barbara Bartolini; Martina Rueca; Cesare Ernesto Maria Gruber; Francesco Messina; Emanuela Giombini; Giuseppe Ippolito; Maria Rosaria Capobianchi; Antonino Di Caro. The newly introduced SARS-CoV-2 variant A222V is rapidly spreading in Lazio region, Italy. 2020, 1 .

AMA Style

Barbara Bartolini, Martina Rueca, Cesare Ernesto Maria Gruber, Francesco Messina, Emanuela Giombini, Giuseppe Ippolito, Maria Rosaria Capobianchi, Antonino Di Caro. The newly introduced SARS-CoV-2 variant A222V is rapidly spreading in Lazio region, Italy. . 2020; ():1.

Chicago/Turabian Style

Barbara Bartolini; Martina Rueca; Cesare Ernesto Maria Gruber; Francesco Messina; Emanuela Giombini; Giuseppe Ippolito; Maria Rosaria Capobianchi; Antonino Di Caro. 2020. "The newly introduced SARS-CoV-2 variant A222V is rapidly spreading in Lazio region, Italy." , no. : 1.

Journal article
Published: 13 September 2020 in Viruses
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The Republic of Congo (RoC) declared a chikungunya (CHIK) outbreak on 9 February 2019. We conducted a ONE-Human-Animal HEALTH epidemiological, virological and entomological investigation. Methods: We collected national surveillance and epidemiological data. CHIK diagnosis was based on RT-PCR and CHIKV-specific antibodies. Full CHIKV genome sequences were obtained by Sanger and MinION approaches and Bayesian tree phylogenetic analysis was performed. Mosquito larvae and 215 adult mosquitoes were collected in different villages of Kouilou and Pointe-Noire districts and estimates of Aedes (Ae.) mosquitos’ CHIKV-infectious bites obtained. We found two new CHIKV sequences of the East/Central/South African (ECSA) lineage, clustering with the recent enzootic sub-clade 2, showing the A226V mutation. The RoC 2019 CHIKV strain has two novel mutations, E2-T126M and E2-H351N. Phylogenetic suggests a common origin from 2016 Angola strain, from which it diverged around 1989 (95% HPD 1985–1994). The infectious bite pattern was similar for 2017, 2018 and early 2019. One Ae. albopictus pool was RT-PCR positive. The 2019 RoC CHIKV strain seems to be recently introduced or be endemic in sylvatic cycle. Distinct from the contemporary Indian CHIKV isolates and in contrast to the original Central-African strains (transmitted by Ae. aegypti), it carries the A226V mutation, indicating an independent adaptive mutation in response to vector replacement (Ae. albopictus vs Ae. aegypti).

ACS Style

Francesco Vairo; Martin Aimè Coussoud-Mavoungou; Francine Ntoumi; Concetta Castilletti; Lambert Kitembo; Najmul Haider; Fabrizio Carletti; Francesca Colavita; Cesare Gruber; Marco Iannetta; Francesco Messina; Simone Lanini; Biez Ulrich Judicaël; Emanuela Giombini; Chiara Montaldo; Chantal Portella; Steve Diafouka-Diatela; Martina Rueca; Richard Kock; Barbara Bartolini; Leonard Mboera; Vincent Munster; Robert Fischer; Stephanie Seifert; César Muñoz-Fontela; Beatriz Escudero-Pérez; Sergio Gomez-Medina; Emily Nelson; Patrick Kjia Tungu; Emanuele Nicastri; Vincenzo Puro; Antonino Di Caro; Maria Capobianchi; Jacqueline Mikolo; Alimuddin Zumla; Giuseppe Ippolito; on behalf of the Pandora-ID-NET Consortium Chikungunya Outbreak Group Taskforce. Chikungunya Outbreak in the Republic of the Congo, 2019—Epidemiological, Virological and Entomological Findings of a South-North Multidisciplinary Taskforce Investigation. Viruses 2020, 12, 1020 .

AMA Style

Francesco Vairo, Martin Aimè Coussoud-Mavoungou, Francine Ntoumi, Concetta Castilletti, Lambert Kitembo, Najmul Haider, Fabrizio Carletti, Francesca Colavita, Cesare Gruber, Marco Iannetta, Francesco Messina, Simone Lanini, Biez Ulrich Judicaël, Emanuela Giombini, Chiara Montaldo, Chantal Portella, Steve Diafouka-Diatela, Martina Rueca, Richard Kock, Barbara Bartolini, Leonard Mboera, Vincent Munster, Robert Fischer, Stephanie Seifert, César Muñoz-Fontela, Beatriz Escudero-Pérez, Sergio Gomez-Medina, Emily Nelson, Patrick Kjia Tungu, Emanuele Nicastri, Vincenzo Puro, Antonino Di Caro, Maria Capobianchi, Jacqueline Mikolo, Alimuddin Zumla, Giuseppe Ippolito, on behalf of the Pandora-ID-NET Consortium Chikungunya Outbreak Group Taskforce. Chikungunya Outbreak in the Republic of the Congo, 2019—Epidemiological, Virological and Entomological Findings of a South-North Multidisciplinary Taskforce Investigation. Viruses. 2020; 12 (9):1020.

Chicago/Turabian Style

Francesco Vairo; Martin Aimè Coussoud-Mavoungou; Francine Ntoumi; Concetta Castilletti; Lambert Kitembo; Najmul Haider; Fabrizio Carletti; Francesca Colavita; Cesare Gruber; Marco Iannetta; Francesco Messina; Simone Lanini; Biez Ulrich Judicaël; Emanuela Giombini; Chiara Montaldo; Chantal Portella; Steve Diafouka-Diatela; Martina Rueca; Richard Kock; Barbara Bartolini; Leonard Mboera; Vincent Munster; Robert Fischer; Stephanie Seifert; César Muñoz-Fontela; Beatriz Escudero-Pérez; Sergio Gomez-Medina; Emily Nelson; Patrick Kjia Tungu; Emanuele Nicastri; Vincenzo Puro; Antonino Di Caro; Maria Capobianchi; Jacqueline Mikolo; Alimuddin Zumla; Giuseppe Ippolito; on behalf of the Pandora-ID-NET Consortium Chikungunya Outbreak Group Taskforce. 2020. "Chikungunya Outbreak in the Republic of the Congo, 2019—Epidemiological, Virological and Entomological Findings of a South-North Multidisciplinary Taskforce Investigation." Viruses 12, no. 9: 1020.

Journal article
Published: 26 August 2020 in Microorganisms
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We report whole-genome and intra-host variability of SARS-Cov-2 assessed by next generation sequencing (NGS) in upper (URT) and lower respiratory tract (LRT) from COVID-19 patients. The aim was to identify possible tissue-specific patterns and signatures of variant selection for each respiratory compartment. Six patients, admitted to the Intensive Care Unit, were included in the study. Thirteen URT and LRT were analyzed by NGS amplicon-based approach on Ion Torrent Platform. Bioinformatic analysis was performed using both realized in-house and supplied by ThermoFisher programs. Phylogenesis showed clade V clustering of the first patients diagnosed in Italy, and clade G for later strains. The presence of quasispecies was observed, with variants uniformly distributed along the genome and frequency of minority variants spanning from 1% to ~30%. For each patient, the patterns of variants in URT and LRT were profoundly different, indicating compartmentalized virus replication. No clear variant signature and no significant difference in nucleotide diversity between LRT and URT were observed. SARS-CoV-2 presents genetic heterogeneity and quasispecies compartmentalization in URT and LRT. Intra-patient diversity was low. The pattern of minority variants was highly heterogeneous and no specific district signature could be identified, nevertheless, analysis of samples, longitudinally collected in patients, supported quasispecies evolution.

ACS Style

Martina Rueca; Barbara Bartolini; Cesare Gruber; Antonio Piralla; Fausto Baldanti; Emanuela Giombini; Francesco Messina; Luisa Marchioni; Giuseppe Ippolito; Antonino Di Caro; Maria Capobianchi. Compartmentalized Replication of SARS-Cov-2 in Upper vs. Lower Respiratory Tract Assessed by Whole Genome Quasispecies Analysis. Microorganisms 2020, 8, 1302 .

AMA Style

Martina Rueca, Barbara Bartolini, Cesare Gruber, Antonio Piralla, Fausto Baldanti, Emanuela Giombini, Francesco Messina, Luisa Marchioni, Giuseppe Ippolito, Antonino Di Caro, Maria Capobianchi. Compartmentalized Replication of SARS-Cov-2 in Upper vs. Lower Respiratory Tract Assessed by Whole Genome Quasispecies Analysis. Microorganisms. 2020; 8 (9):1302.

Chicago/Turabian Style

Martina Rueca; Barbara Bartolini; Cesare Gruber; Antonio Piralla; Fausto Baldanti; Emanuela Giombini; Francesco Messina; Luisa Marchioni; Giuseppe Ippolito; Antonino Di Caro; Maria Capobianchi. 2020. "Compartmentalized Replication of SARS-Cov-2 in Upper vs. Lower Respiratory Tract Assessed by Whole Genome Quasispecies Analysis." Microorganisms 8, no. 9: 1302.

Journal article
Published: 11 October 2019 in Journal of Antimicrobial Chemotherapy
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BackgroundAntiretroviral drug resistance mutations remain a major cause of treatment failure.ObjectivesTo evaluate the impact of NRTI resistance mutations on virological effectiveness of elvitegravir-containing regimens.Materials and methodsWe selected treatment-experienced HIV-1-infected patients starting elvitegravir/cobicistat/emtricitabine/tenofovir alafenamide (E/C/F/TAF) or elvitegravir/cobicistat/emtricitabine/tenofovir disoproxil fumarate (E/C/F/TDF), with at least one protease/reverse transcriptase genotype available before switching and at least one HIV-1 RNA viral load (VL) measurement during follow-up. The primary endpoint was virological failure (VF), defined as one VL value of ≥1000 copies/mL or two consecutive VL values of >50 copies/mL.ResultsWe included 264 ART regimens: 75.6% male, median (IQR) age 47 years (39–53), 7 years (3–16) of HIV infection, nadir CD4+ 247 cells/mm3 (105–361), 81.5% with VL ≤50 copies/mL and 11.7% with at least one NRTI mutation at baseline. Eleven (5.2%) VFs occurred in virologically suppressed patients versus eight (15.1%) in viraemic patients. The estimated probability of VF at 48 weeks with versus without any NRTI mutation was 7.4% (95% CI 2.3–12.5) versus 3.8% (2.1–5.5) in virologically suppressed patients and 66.7% (39.5–93.9) versus 11.2% (6.5–15.9) (P<0.001) in viraemic patients. The only predictor of VF was time on therapy (per 1 year more, adjusted HR 1.14, 95% CI 1.02–1.27, P=0.024) in viraemic patients.ConclusionsA switch to E/C/F/TDF or E/C/F/TAF is safe for virologically suppressed patients without documented NRTI resistance, but not recommended in viraemic patients with a history of NRTI resistance. Although we did not detect a detrimental effect of past NRTI resistance in virologically suppressed patients, a fully active regimen remains preferred in this setting due to possible rebound of drug-resistant virus in the long term.

ACS Style

Sara Modica; David Redi; Roberta Gagliardini; Emanuela Giombini; Antonia Bezenchek; Domenico Di Carlo; Franco Maggiolo; Francesca Lombardi; Alberto Borghetti; Damiano Farinacci; Annapaola Callegaro; Maria R Gismondo; Manuela Colafigli; Gaetana Sterrantino; Andrea Costantini; Sergio M Ferrara; Stefano Rusconi; Maurizio Zazzi; Barbara Rossetti; Andrea De Luca; Nicola Gianotti. Impact of NRTI resistance mutations on virological effectiveness of antiretroviral regimens containing elvitegravir: a multi-cohort study. Journal of Antimicrobial Chemotherapy 2019, 75, 194 -199.

AMA Style

Sara Modica, David Redi, Roberta Gagliardini, Emanuela Giombini, Antonia Bezenchek, Domenico Di Carlo, Franco Maggiolo, Francesca Lombardi, Alberto Borghetti, Damiano Farinacci, Annapaola Callegaro, Maria R Gismondo, Manuela Colafigli, Gaetana Sterrantino, Andrea Costantini, Sergio M Ferrara, Stefano Rusconi, Maurizio Zazzi, Barbara Rossetti, Andrea De Luca, Nicola Gianotti. Impact of NRTI resistance mutations on virological effectiveness of antiretroviral regimens containing elvitegravir: a multi-cohort study. Journal of Antimicrobial Chemotherapy. 2019; 75 (1):194-199.

Chicago/Turabian Style

Sara Modica; David Redi; Roberta Gagliardini; Emanuela Giombini; Antonia Bezenchek; Domenico Di Carlo; Franco Maggiolo; Francesca Lombardi; Alberto Borghetti; Damiano Farinacci; Annapaola Callegaro; Maria R Gismondo; Manuela Colafigli; Gaetana Sterrantino; Andrea Costantini; Sergio M Ferrara; Stefano Rusconi; Maurizio Zazzi; Barbara Rossetti; Andrea De Luca; Nicola Gianotti. 2019. "Impact of NRTI resistance mutations on virological effectiveness of antiretroviral regimens containing elvitegravir: a multi-cohort study." Journal of Antimicrobial Chemotherapy 75, no. 1: 194-199.

Journal article
Published: 01 August 2019 in Infection and Drug Resistance
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The Ralstonia spp. genus is a group of non-fermentative, Gram-negative bacteria often resistant to many antibiotics, which are emerging as opportunistic pathogens frequently associated with infections in hospital settings. We present herein a case of combined R. pickettii and R. mannitolilytica persisting and relapsing bacteraemia, possibly caused by a septic arterial thrombosis secondary to the rupture of an internal carotid artery aneurysm. Microbiology studies showed that both Ralstonia isolates produced biofilm and carried class D oxacillinase genes. When confronted with infections caused by members of the Ralstonia genus, identification to the species level is crucial for correct clinical management, as the two species show different antibiotic susceptibility patterns.

ACS Style

Monica Basso; Carolina Venditti; Giammarco Raponi; Anna Sara Navazio; Francesco Alessandri; Emanuela Giombini; Carla Nisii; Antonino Di Caro; Mario Venditti. A case of persistent bacteraemia by Ralstonia mannitolilytica and Ralstonia pickettii in an intensive care unit. Infection and Drug Resistance 2019, ume 12, 2391 -2395.

AMA Style

Monica Basso, Carolina Venditti, Giammarco Raponi, Anna Sara Navazio, Francesco Alessandri, Emanuela Giombini, Carla Nisii, Antonino Di Caro, Mario Venditti. A case of persistent bacteraemia by Ralstonia mannitolilytica and Ralstonia pickettii in an intensive care unit. Infection and Drug Resistance. 2019; ume 12 ():2391-2395.

Chicago/Turabian Style

Monica Basso; Carolina Venditti; Giammarco Raponi; Anna Sara Navazio; Francesco Alessandri; Emanuela Giombini; Carla Nisii; Antonino Di Caro; Mario Venditti. 2019. "A case of persistent bacteraemia by Ralstonia mannitolilytica and Ralstonia pickettii in an intensive care unit." Infection and Drug Resistance ume 12, no. : 2391-2395.

Journal article
Published: 13 June 2019 in Epidemics
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A major outbreak of Hepatitis A Virus (HAV) has swept through Europe between mid-2016 and 2017, mainly within the community of men who have sex with men (MSM). Over the same period, about 1000 outbreak-related cases of acute Hepatitis A (AHA) were recorded in Lazio region, Italy. We calibrated a Bayesian model to reconstruct likely transmission events within all 44 households where multiple infections were recorded, representing a total of 103 cases from the HAV outbreak in Lazio. Based on information on the observed times of symptom onset, we estimated the probability distribution function of the HAV generation time and used it to compute the effective and instantaneous reproduction numbers for the considered outbreak from the overall epidemic curve (N = 998 cases). We estimated a mean generation time of 30.2 days (95%CI: 25.2-33.0) and an effective reproduction number of about 1.63 (95% CI: 1.35-1.94). Transmissibility peaked in January 2017, shortly before targeted awareness and vaccination campaigns were put in place by health authorities; however, transmission remained above the epidemic threshold until June 2017. Within households, children (0-15) and young adults (16-30) infected preferentially individuals of the same age class, whereas transmission within older age groups was substantially homogeneous. These results suggest that the implemented interventions were able to slow down HAV transmission, but not to bring it rapidly to a halt. According to our estimates of the HAV transmissibility, about 50% of the at-risk persons should be immunized to prevent similar outbreaks in the future. Our results also indicate spillover from community transmission to household members, suggesting the opportunity of vaccinating household contacts of cases to prevent further spread of the epidemics.

ACS Style

Giorgio Guzzetta; Claudia Minosse; Raffaella Pisapia; Emanuela Giombini; Alessia Mammone; Francesco Vairo; Anna Rosa Garbuglia; Paola Scognamiglio; Maria Rosaria Capobianchi; Stefano Merler; Giuseppe Ippolito; Simone Lanini. Household transmission and disease transmissibility of a large HAV outbreak in Lazio, Italy, 2016–2017. Epidemics 2019, 29, 100351 .

AMA Style

Giorgio Guzzetta, Claudia Minosse, Raffaella Pisapia, Emanuela Giombini, Alessia Mammone, Francesco Vairo, Anna Rosa Garbuglia, Paola Scognamiglio, Maria Rosaria Capobianchi, Stefano Merler, Giuseppe Ippolito, Simone Lanini. Household transmission and disease transmissibility of a large HAV outbreak in Lazio, Italy, 2016–2017. Epidemics. 2019; 29 ():100351.

Chicago/Turabian Style

Giorgio Guzzetta; Claudia Minosse; Raffaella Pisapia; Emanuela Giombini; Alessia Mammone; Francesco Vairo; Anna Rosa Garbuglia; Paola Scognamiglio; Maria Rosaria Capobianchi; Stefano Merler; Giuseppe Ippolito; Simone Lanini. 2019. "Household transmission and disease transmissibility of a large HAV outbreak in Lazio, Italy, 2016–2017." Epidemics 29, no. : 100351.

Original paper
Published: 08 April 2019 in Infection
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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. Sixteen samples from HBV co-infected Sudanese patients detected by multiplex-nested PCR, were amplified targeting the P/S region and sequenced by UDPS. 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). Overall, UDPS is more effective than multiplex-nested PCR for identifying multiple HBV genotypes and subtypes infections.

ACS Style

Khalid Abdallah Enan; Claudia Minosse; Abdel Rahim Mohammed El Hussein; Marina Selleri; Emanuela Giombini; Maria Rosaria Capobianchi; Isam Mohamed Elkhidir; Mohamed Omer Mustafa; Osama Mohamed Khair; Dina Ahamed Hassan; Anna Rosa Garbuglia. Analysis of hepatitis B virus-mixed genotype infection by ultra deep pyrosequencing in Sudanese patients, 2015–2016. Infection 2019, 47, 793 -803.

AMA Style

Khalid Abdallah Enan, Claudia Minosse, Abdel Rahim Mohammed El Hussein, Marina Selleri, Emanuela Giombini, Maria Rosaria Capobianchi, Isam Mohamed Elkhidir, Mohamed Omer Mustafa, Osama Mohamed Khair, Dina Ahamed Hassan, Anna Rosa Garbuglia. Analysis of hepatitis B virus-mixed genotype infection by ultra deep pyrosequencing in Sudanese patients, 2015–2016. Infection. 2019; 47 (5):793-803.

Chicago/Turabian Style

Khalid Abdallah Enan; Claudia Minosse; Abdel Rahim Mohammed El Hussein; Marina Selleri; Emanuela Giombini; Maria Rosaria Capobianchi; Isam Mohamed Elkhidir; Mohamed Omer Mustafa; Osama Mohamed Khair; Dina Ahamed Hassan; Anna Rosa Garbuglia. 2019. "Analysis of hepatitis B virus-mixed genotype infection by ultra deep pyrosequencing in Sudanese patients, 2015–2016." Infection 47, no. 5: 793-803.

Original research
Published: 01 November 2018 in Infection and Drug Resistance
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Clinical and virological properties of hepatitis C virus genotype 4 infection in patients treated with different direct-acting antiviral agents 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

ACS Style

Claudia Minosse; Marina Selleri; Emanuela Giombini; Barbara Bartolini; Maria Rosaria Capobianchi; Stefano Cerilli; Laura Loiacono; Chiara Taibi; Gianpiero D'Offizi; Fiona McPhee; Anna Rosa Garbuglia. Clinical and virological properties of hepatitis C virus genotype 4 infection in patients treated with different direct-acting antiviral agents. Infection and Drug Resistance 2018, ume 11, 2117 -2127.

AMA Style

Claudia Minosse, Marina Selleri, Emanuela Giombini, Barbara Bartolini, Maria Rosaria Capobianchi, Stefano Cerilli, Laura Loiacono, Chiara Taibi, Gianpiero D'Offizi, Fiona McPhee, Anna Rosa Garbuglia. Clinical and virological properties of hepatitis C virus genotype 4 infection in patients treated with different direct-acting antiviral agents. Infection and Drug Resistance. 2018; ume 11 ():2117-2127.

Chicago/Turabian Style

Claudia Minosse; Marina Selleri; Emanuela Giombini; Barbara Bartolini; Maria Rosaria Capobianchi; Stefano Cerilli; Laura Loiacono; Chiara Taibi; Gianpiero D'Offizi; Fiona McPhee; Anna Rosa Garbuglia. 2018. "Clinical and virological properties of hepatitis C virus genotype 4 infection in patients treated with different direct-acting antiviral agents." Infection and Drug Resistance ume 11, no. : 2117-2127.

Journal article
Published: 06 October 2018 in Viruses
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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.

ACS Style

Cesare E. M. Gruber; Emanuela Giombini; Marina Selleri; Simon H. Tausch; Andreas Andrusch; Alona Tyshaieva; Giusy Cardeti; Raniero Lorenzetti; Lorenzo De Marco; Fabrizio Carletti; Andreas Nitsche; Maria R. Capobianchi; Giuseppe Ippolito; Gian Luca Autorino; Concetta Castilletti. Whole Genome Characterization of Orthopoxvirus (OPV) Abatino, a Zoonotic Virus Representing a Putative Novel Clade of Old World Orthopoxviruses. Viruses 2018, 10, 546 .

AMA Style

Cesare E. M. Gruber, Emanuela Giombini, Marina Selleri, Simon H. Tausch, Andreas Andrusch, Alona Tyshaieva, Giusy Cardeti, Raniero Lorenzetti, Lorenzo De Marco, Fabrizio Carletti, Andreas Nitsche, Maria R. Capobianchi, Giuseppe Ippolito, Gian Luca Autorino, Concetta Castilletti. Whole Genome Characterization of Orthopoxvirus (OPV) Abatino, a Zoonotic Virus Representing a Putative Novel Clade of Old World Orthopoxviruses. Viruses. 2018; 10 (10):546.

Chicago/Turabian Style

Cesare E. M. Gruber; Emanuela Giombini; Marina Selleri; Simon H. Tausch; Andreas Andrusch; Alona Tyshaieva; Giusy Cardeti; Raniero Lorenzetti; Lorenzo De Marco; Fabrizio Carletti; Andreas Nitsche; Maria R. Capobianchi; Giuseppe Ippolito; Gian Luca Autorino; Concetta Castilletti. 2018. "Whole Genome Characterization of Orthopoxvirus (OPV) Abatino, a Zoonotic Virus Representing a Putative Novel Clade of Old World Orthopoxviruses." Viruses 10, no. 10: 546.

Journal article
Published: 01 December 2017 in Emerging Infectious Diseases
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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.

ACS Style

Giusy Cardeti; Cesare E. M. Gruber; Claudia Eleni; Fabrizio Carletti; Concetta Castilletti; Giuseppe Manna; Francesca Rosone; Emanuela Giombini; Marina Selleri; Daniele Lapa; Vincenzo Puro; Antonino Di Caro; Raniero Lorenzetti; Maria Teresa Scicluna; Goffredo Grifoni; Annapaola Rizzoli; Valentina Tagliapietra; Lorenzo De Marco; Maria Rosaria Capobianchi; Gian Luca Autorino. Fatal Outbreak in Tonkean Macaques Caused by Possibly Novel Orthopoxvirus, Italy, January 20151. Emerging Infectious Diseases 2017, 23, 1941 -1949.

AMA Style

Giusy Cardeti, Cesare E. M. Gruber, Claudia Eleni, Fabrizio Carletti, Concetta Castilletti, Giuseppe Manna, Francesca Rosone, Emanuela Giombini, Marina Selleri, Daniele Lapa, Vincenzo Puro, Antonino Di Caro, Raniero Lorenzetti, Maria Teresa Scicluna, Goffredo Grifoni, Annapaola Rizzoli, Valentina Tagliapietra, Lorenzo De Marco, Maria Rosaria Capobianchi, Gian Luca Autorino. Fatal Outbreak in Tonkean Macaques Caused by Possibly Novel Orthopoxvirus, Italy, January 20151. Emerging Infectious Diseases. 2017; 23 (12):1941-1949.

Chicago/Turabian Style

Giusy Cardeti; Cesare E. M. Gruber; Claudia Eleni; Fabrizio Carletti; Concetta Castilletti; Giuseppe Manna; Francesca Rosone; Emanuela Giombini; Marina Selleri; Daniele Lapa; Vincenzo Puro; Antonino Di Caro; Raniero Lorenzetti; Maria Teresa Scicluna; Goffredo Grifoni; Annapaola Rizzoli; Valentina Tagliapietra; Lorenzo De Marco; Maria Rosaria Capobianchi; Gian Luca Autorino. 2017. "Fatal Outbreak in Tonkean Macaques Caused by Possibly Novel Orthopoxvirus, Italy, January 20151." Emerging Infectious Diseases 23, no. 12: 1941-1949.

Case reports
Published: 01 October 2017 in Emerging Infectious Diseases
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In Italy in 2016, acute flaccid myelitis developed in a woman who had received a hematopoietic stem cell transplant. Enterovirus D68 viral genome was detected in respiratory and cerebrospinal fluid samples, and the viral protein 1 sequence clustered with lineage B3. Immunocompromised adults may be at risk for enterovirus D68–associated neurologic complications.

ACS Style

Emanuela Giombini; Martina Rueca; Walter Barberi; Anna Paola Iori; Concetta Castilletti; Paola Scognamiglio; Francesco Vairo; Giuseppe Ippolito; Maria Rosaria Capobianchi; Maria Beatrice Valli. Enterovirus D68–Associated Acute Flaccid Myelitis in Immunocompromised Woman, Italy. Emerging Infectious Diseases 2017, 23, 1690 -1693.

AMA Style

Emanuela Giombini, Martina Rueca, Walter Barberi, Anna Paola Iori, Concetta Castilletti, Paola Scognamiglio, Francesco Vairo, Giuseppe Ippolito, Maria Rosaria Capobianchi, Maria Beatrice Valli. Enterovirus D68–Associated Acute Flaccid Myelitis in Immunocompromised Woman, Italy. Emerging Infectious Diseases. 2017; 23 (10):1690-1693.

Chicago/Turabian Style

Emanuela Giombini; Martina Rueca; Walter Barberi; Anna Paola Iori; Concetta Castilletti; Paola Scognamiglio; Francesco Vairo; Giuseppe Ippolito; Maria Rosaria Capobianchi; Maria Beatrice Valli. 2017. "Enterovirus D68–Associated Acute Flaccid Myelitis in Immunocompromised Woman, Italy." Emerging Infectious Diseases 23, no. 10: 1690-1693.

Journal article
Published: 07 August 2017 in Viruses
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Hepatitis C virus (HCV) genotype (GT)3 is associated with increased risk of steatosis, development of cirrhosis and hepatocellular carcinoma. Limited data are available regarding genetic variability and use of direct-acting antiviral agents in these patients. non-structural protein 5A (NS5A) and non-structural protein 5B (NS5B) sequencing was performed on 45 HCV GT3-infected Italian patients subsequently treated with sofosbuvir ± daclatasvir (SOF ± DCV). Novel GT3a polymorphisms were observed by Sanger sequencing in three NS5A (T79S, T107K, and T107S) and three NS5B (G166R, Q180K, and C274W) baseline sequences in patients who achieved sustained virological response (SVR). Baseline NS5A resistance-associated substitutions A30K and Y93H were detected in 9.5% of patients; one patient with A30K did not achieve SVR. Phylogenetic analyses of sequences showed no distinct clustering. Genetic heterogeneity of NS5A and NS5B was evaluated using ultra-deep pyrosequencing (UDPS) in samples longitudinally collected in patients not achieving SVR. Some novel NS5A and NS5B polymorphisms detected at baseline may not impact treatment outcome, as they were not enriched in post-failure samples. In contrast, the novel L31F NS5A variant emerged in one treatment failure, and I184T, G188D and N310S, located on the same NS5B haplotype, became predominant after failure. These findings suggest a potential impact of these novel substitutions on the treatment outcome; however, their significance requires further investigation.

ACS Style

Barbara Bartolini; Emanuela Giombini; Chiara Taibi; Raffaella Lionetti; Marzia Montalbano; Ubaldo Visco-Comandini; Gianpiero D’Offizi; Maria Rosaria Capobianchi; Fiona McPhee; Anna Rosa Garbuglia. Characterization of Naturally Occurring NS5A and NS5B Polymorphisms in Patients Infected with HCV Genotype 3a Treated with Direct-Acting Antiviral Agents. Viruses 2017, 9, 212 .

AMA Style

Barbara Bartolini, Emanuela Giombini, Chiara Taibi, Raffaella Lionetti, Marzia Montalbano, Ubaldo Visco-Comandini, Gianpiero D’Offizi, Maria Rosaria Capobianchi, Fiona McPhee, Anna Rosa Garbuglia. Characterization of Naturally Occurring NS5A and NS5B Polymorphisms in Patients Infected with HCV Genotype 3a Treated with Direct-Acting Antiviral Agents. Viruses. 2017; 9 (8):212.

Chicago/Turabian Style

Barbara Bartolini; Emanuela Giombini; Chiara Taibi; Raffaella Lionetti; Marzia Montalbano; Ubaldo Visco-Comandini; Gianpiero D’Offizi; Maria Rosaria Capobianchi; Fiona McPhee; Anna Rosa Garbuglia. 2017. "Characterization of Naturally Occurring NS5A and NS5B Polymorphisms in Patients Infected with HCV Genotype 3a Treated with Direct-Acting Antiviral Agents." Viruses 9, no. 8: 212.

Journal article
Published: 09 January 2017 in The new microbiologica
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ACS Style

Marina Selleri; Riccardo Dolcetti; Francesca Caccuri; Emanuela Giombini; Gabriella Rozera; Isabella Abbate; Alessia Mammone; Stefania Zanussi; Debora Martorelli; Simona Fiorentini; Arnaldo Caruso; Maria Rosaria Capobianchi. In-depth analysis of compartmentalization of HIV-1 matrix protein p17 in PBMC and plasma. The new microbiologica 2017, 40, 1 .

AMA Style

Marina Selleri, Riccardo Dolcetti, Francesca Caccuri, Emanuela Giombini, Gabriella Rozera, Isabella Abbate, Alessia Mammone, Stefania Zanussi, Debora Martorelli, Simona Fiorentini, Arnaldo Caruso, Maria Rosaria Capobianchi. In-depth analysis of compartmentalization of HIV-1 matrix protein p17 in PBMC and plasma. The new microbiologica. 2017; 40 (1):1.

Chicago/Turabian Style

Marina Selleri; Riccardo Dolcetti; Francesca Caccuri; Emanuela Giombini; Gabriella Rozera; Isabella Abbate; Alessia Mammone; Stefania Zanussi; Debora Martorelli; Simona Fiorentini; Arnaldo Caruso; Maria Rosaria Capobianchi. 2017. "In-depth analysis of compartmentalization of HIV-1 matrix protein p17 in PBMC and plasma." The new microbiologica 40, no. 1: 1.

Journal article
Published: 07 October 2016 in International Journal of Molecular Sciences
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Hepatitis C virus (HCV) is classified into seven phylogenetically distinct genotypes, which are further subdivided into related subtypes. Accurate assignment of genotype/subtype is mandatory in the era of directly acting antivirals. Several molecular methods are available for HCV genotyping; however, a relevant number of samples with indeterminate, mixed, or unspecified subtype results, or even with misclassified genotypes, may occur. Using NS5B direct (DS) and ultra-deep pyrosequencing (UDPS), we have tested 43 samples, which resulted in genotype 1 unsubtyped (n = 17), mixed infection (n = 17), or indeterminate (n = 9) with the Abbott RealTime HCV Genotype II assay. Genotype 1 was confirmed in 14/17 samples (82%): eight resulted in subtype 1b, and five resulted in subtype 1a with both DS and UDPS, while one was classified as subtype 1e by DS and mixed infection (1e + 1a) by UDPS. Three of seventeen genotype 1 samples resulted in genotype 3h with both sequencing approaches. Only one mixed infection was confirmed by UDPS (4d + 1a), while in 88% of cases a single component of the mixture was detected (five genotype 1a, four genotype 1b, two genotype 3a, two genotype 4m, and two genotype 4d); 44% of indeterminate samples resulted genotype 2c by both DS and UDPS, 22% resulted genotype 3a; one indeterminate sample by Abbott resulted in genotype 4d, one resulted in genotype 6n, and one was classified as subtype 3a by DS, and resulted mixed infection (3a + 3h) by UDPS. The concordance between DS and UDPS was 94%, 88%, and 89% for genotype 1, co-infection, and indeterminate results, respectively. UDPS should be considered very useful to resolve ambiguous HCV genotyping results.

ACS Style

Claudia Minosse; Emanuela Giombini; Barbara Bartolini; Maria R. Capobianchi; Anna R. Garbuglia. Ultra-Deep Sequencing Characterization of HCV Samples with Equivocal Typing Results Determined with a Commercial Assay. International Journal of Molecular Sciences 2016, 17, 1679 .

AMA Style

Claudia Minosse, Emanuela Giombini, Barbara Bartolini, Maria R. Capobianchi, Anna R. Garbuglia. Ultra-Deep Sequencing Characterization of HCV Samples with Equivocal Typing Results Determined with a Commercial Assay. International Journal of Molecular Sciences. 2016; 17 (10):1679.

Chicago/Turabian Style

Claudia Minosse; Emanuela Giombini; Barbara Bartolini; Maria R. Capobianchi; Anna R. Garbuglia. 2016. "Ultra-Deep Sequencing Characterization of HCV Samples with Equivocal Typing Results Determined with a Commercial Assay." International Journal of Molecular Sciences 17, no. 10: 1679.

Research article
Published: 17 May 2016 in PLOS ONE
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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.

ACS Style

Claudia Caglioti; Marina Selleri; Gabriella Rozera; Emanuela Giombini; Paola Zaccaro; Maria Beatrice Valli; Maria Rosaria Capobianchi. In-Depth Analysis of HA and NS1 Genes in A(H1N1)pdm09 Infected Patients. PLOS ONE 2016, 11, e0155661 .

AMA Style

Claudia Caglioti, Marina Selleri, Gabriella Rozera, Emanuela Giombini, Paola Zaccaro, Maria Beatrice Valli, Maria Rosaria Capobianchi. In-Depth Analysis of HA and NS1 Genes in A(H1N1)pdm09 Infected Patients. PLOS ONE. 2016; 11 (5):e0155661.

Chicago/Turabian Style

Claudia Caglioti; Marina Selleri; Gabriella Rozera; Emanuela Giombini; Paola Zaccaro; Maria Beatrice Valli; Maria Rosaria Capobianchi. 2016. "In-Depth Analysis of HA and NS1 Genes in A(H1N1)pdm09 Infected Patients." PLOS ONE 11, no. 5: e0155661.

Clinical trial
Published: 02 November 2015 in Proceedings of the National Academy of Sciences
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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.

ACS Style

Riccardo Dolcetti; Cinzia Giagulli; Wangxiao He; Marina Selleri; Francesca Caccuri; Lindsay M. Eyzaguirre; Pietro Mazzuca; Silvia Corbellini; Federica Campilongo; Stefania Marsico; Emanuela Giombini; Elena Muraro; Gabriella Rozera; Paolo De Paoli; Antonino Carbone; Maria Rosaria Capobianchi; Giuseppe Ippolito; Simona Fiorentini; William A. Blattner; Wuyuan Lu; Robert C. Gallo; Arnaldo Caruso. Role of HIV-1 matrix protein p17 variants in lymphoma pathogenesis. Proceedings of the National Academy of Sciences 2015, 112, 14331 -14336.

AMA Style

Riccardo Dolcetti, Cinzia Giagulli, Wangxiao He, Marina Selleri, Francesca Caccuri, Lindsay M. Eyzaguirre, Pietro Mazzuca, Silvia Corbellini, Federica Campilongo, Stefania Marsico, Emanuela Giombini, Elena Muraro, Gabriella Rozera, Paolo De Paoli, Antonino Carbone, Maria Rosaria Capobianchi, Giuseppe Ippolito, Simona Fiorentini, William A. Blattner, Wuyuan Lu, Robert C. Gallo, Arnaldo Caruso. Role of HIV-1 matrix protein p17 variants in lymphoma pathogenesis. Proceedings of the National Academy of Sciences. 2015; 112 (46):14331-14336.

Chicago/Turabian Style

Riccardo Dolcetti; Cinzia Giagulli; Wangxiao He; Marina Selleri; Francesca Caccuri; Lindsay M. Eyzaguirre; Pietro Mazzuca; Silvia Corbellini; Federica Campilongo; Stefania Marsico; Emanuela Giombini; Elena Muraro; Gabriella Rozera; Paolo De Paoli; Antonino Carbone; Maria Rosaria Capobianchi; Giuseppe Ippolito; Simona Fiorentini; William A. Blattner; Wuyuan Lu; Robert C. Gallo; Arnaldo Caruso. 2015. "Role of HIV-1 matrix protein p17 variants in lymphoma pathogenesis." Proceedings of the National Academy of Sciences 112, no. 46: 14331-14336.

Case reports
Published: 29 July 2015 in Journal of Clinical Virology
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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. 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. 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. 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.

ACS Style

Barbara Bartolini; Marina Selleri; Anna Rosa Garbuglia; Emanuela Giombini; Chiara Taibi; Raffaella Lionetti; Gianpiero D'Offizi; Maria R. Capobianchi. HCV NS3 quasispecies in liver and plasma and dynamics of telaprevir-resistant variants in breakthrough patients assessed by UDPS: A case study. Journal of Clinical Virology 2015, 72, 60 -65.

AMA Style

Barbara Bartolini, Marina Selleri, Anna Rosa Garbuglia, Emanuela Giombini, Chiara Taibi, Raffaella Lionetti, Gianpiero D'Offizi, Maria R. Capobianchi. HCV NS3 quasispecies in liver and plasma and dynamics of telaprevir-resistant variants in breakthrough patients assessed by UDPS: A case study. Journal of Clinical Virology. 2015; 72 ():60-65.

Chicago/Turabian Style

Barbara Bartolini; Marina Selleri; Anna Rosa Garbuglia; Emanuela Giombini; Chiara Taibi; Raffaella Lionetti; Gianpiero D'Offizi; Maria R. Capobianchi. 2015. "HCV NS3 quasispecies in liver and plasma and dynamics of telaprevir-resistant variants in breakthrough patients assessed by UDPS: A case study." Journal of Clinical Virology 72, no. : 60-65.

Journal article
Published: 20 May 2015 in Journal of Clinical Virology
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The publisher regrets that an author name was incorrect in the online version of this paper. The name appeared as D’Offizi Gianpiero; however, the correct name is Gianpiero D’Offizi, as shown above. The online version has now been corrected.

ACS Style

Barbara Bartolini; Raffaella Lionetti; Emanuela Giombini; Catia Sias; Chiara Taibi; Marzia Montalbano; Gianpiero D’Offizi; Fiona McPhee; Eric A. Hughes; Nannan Zhou; Giuseppe Ippolito; Anna Rosa Garbuglia; Maria Rosaria Capobianchi. Erratum to ‘Dynamics of HCV genotype 4 resistance-associated variants during virologic escape with pIFN/RBV + daclatasvir: A case study using ultra deep pyrosequencing’ [Journal of Clinical Virology 66 (2015) 38–43]. Journal of Clinical Virology 2015, 69, 252 .

AMA Style

Barbara Bartolini, Raffaella Lionetti, Emanuela Giombini, Catia Sias, Chiara Taibi, Marzia Montalbano, Gianpiero D’Offizi, Fiona McPhee, Eric A. Hughes, Nannan Zhou, Giuseppe Ippolito, Anna Rosa Garbuglia, Maria Rosaria Capobianchi. Erratum to ‘Dynamics of HCV genotype 4 resistance-associated variants during virologic escape with pIFN/RBV + daclatasvir: A case study using ultra deep pyrosequencing’ [Journal of Clinical Virology 66 (2015) 38–43]. Journal of Clinical Virology. 2015; 69 ():252.

Chicago/Turabian Style

Barbara Bartolini; Raffaella Lionetti; Emanuela Giombini; Catia Sias; Chiara Taibi; Marzia Montalbano; Gianpiero D’Offizi; Fiona McPhee; Eric A. Hughes; Nannan Zhou; Giuseppe Ippolito; Anna Rosa Garbuglia; Maria Rosaria Capobianchi. 2015. "Erratum to ‘Dynamics of HCV genotype 4 resistance-associated variants during virologic escape with pIFN/RBV + daclatasvir: A case study using ultra deep pyrosequencing’ [Journal of Clinical Virology 66 (2015) 38–43]." Journal of Clinical Virology 69, no. : 252.