title: Hepatitis C virus quasispecies and pseudotype analysis from acute infection to chronicity in HIV-1 co-infected individuals.
abstract: HIV-1 infected patients who acquire HCV infection have higher rates of chronicity and liver disease progression than patients with HCV mono-infection. Understanding early events in this pathogenic process is important. We applied single genome sequencing of the E1 to NS3 regions and viral pseudotype neutralization assays to explore the consequences of viral quasispecies evolution from pre-seroconversion to chronicity in four co-infected individuals (mean follow up 566 days). We observed that one to three founder viruses were transmitted. Relatively low viral sequence diversity, possibly related to an impaired immune response, due to HIV infection was observed in three patients. However, the fourth patient, after an early purifying selection displayed increasing E2 sequence evolution, possibly related to being on suppressive antiretroviral therapy. Viral pseudotypes generated from HCV variants showed relative resistance to neutralization by autologous plasma but not to plasma collected from later time points, confirming ongoing virus escape from antibody neutralization.
authors.affiliation: Division of Infection & Immunity, Faculty of Medical Sciences, University College London, United Kingdom; Clinical Microbiology & Virology, UCL Hospital NHS Foundation Trust, United Kingdom. Electronic address: r.ferns@ucl.ac.uk.
authors.forename: R Bridget
authors.initials: RB
authors.lastname: Ferns
authors.affiliation: School of Life Sciences & NIHR Biomedical Research Unit in Gastrointestinal & Liver Diseases, Faculty of Medicine and Health Sciences, University of Nottingham, United Kingdom.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Tarr
authors.affiliation: Division of Infection & Immunity, Faculty of Medical Sciences, University College London, United Kingdom.
authors.forename: Stephane
authors.initials: S
authors.lastname: Hue
authors.affiliation: School of Life Sciences & NIHR Biomedical Research Unit in Gastrointestinal & Liver Diseases, Faculty of Medicine and Health Sciences, University of Nottingham, United Kingdom.
authors.forename: Richard A
authors.initials: RA
authors.lastname: Urbanowicz
authors.affiliation: School of Life Sciences & NIHR Biomedical Research Unit in Gastrointestinal & Liver Diseases, Faculty of Medicine and Health Sciences, University of Nottingham, United Kingdom.
authors.forename: C Patrick
authors.initials: CP
authors.lastname: McClure
authors.affiliation: Research Department of Infection and Population Health, University College London, United Kingdom.
authors.forename: Richard
authors.initials: R
authors.lastname: Gilson
authors.affiliation: School of Life Sciences & NIHR Biomedical Research Unit in Gastrointestinal & Liver Diseases, Faculty of Medicine and Health Sciences, University of Nottingham, United Kingdom.
authors.forename: Jonathan K
authors.initials: JK
authors.lastname: Ball
authors.affiliation: Clinical Microbiology & Virology, UCL Hospital NHS Foundation Trust, United Kingdom.
authors.forename: Eleni
authors.initials: E
authors.lastname: Nastouli
authors.affiliation: Division of Infection & Immunity, Faculty of Medical Sciences, University College London, United Kingdom.
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Garson
authors.affiliation: Division of Infection & Immunity, Faculty of Medical Sciences, University College London, United Kingdom; Wellcome Trust Africa Centre for Health and Population Sciences, University of KwaZulu, Natal, South Africa.
authors.forename: Deenan
authors.initials: D
authors.lastname: Pillay
mesh_terms: D000208:Acute Disease; D000328:Adult; D000914:Antibodies, Viral / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000821:virology; D002908:Chronic Disease; D060085:Coinfection; D018450:Disease Progression; D000939:Epitopes / Q000235:genetics / Q000276:immunology; D015870:Gene Expression; D015658:HIV Infections / Q000276:immunology / Q000473:pathology / Q000821:virology; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology* / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000473:pathology / Q000821:virology; D006801:Humans; D057131:Immune Evasion; D008297:Male; D008875:Middle Aged; D058889:Molecular Typing; D009154:Mutation; D009500:Neutralization Tests; D010802:Phylogeny; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology / Q000473:pathology / Q000821:virology; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology / Q000473:pathology / Q000821:virology; D014759:Viral Envelope Proteins / Q000235:genetics* / Q000276:immunology; D017361:Viral Nonstructural Proteins / Q000235:genetics* / Q000276:immunology; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
chemical_list: D000914:Antibodies, Viral; D000939:Epitopes; D014759:Viral Envelope Proteins; D017361:Viral Nonstructural Proteins; C087035:E1 protein, Hepatitis C virus; C084422:NS3 protein, hepatitis C virus; D012697:Serine Endopeptidases; D043583:Nucleoside-Triphosphatase; D053487:DEAD-box RNA Helicases; D000085242:Viral Proteases
keywords: Antiretroviral therapy; Founder virus; HCV pseudotype neutralization; HCV quasispecies; HIV-1 co-infection; Single genome sequencing