title: Human serum facilitates hepatitis C virus infection, and neutralizing responses inversely correlate with viral replication kinetics at the acute phase of hepatitis C virus infection.
abstract: The factors leading to spontaneous clearance of hepatitis C virus (HCV) or to viral persistence are elusive. Understanding virus-host interactions that enable acute HCV clearance is key to the development of more effective therapeutic and prophylactic strategies. Here, using a sensitive neutralization assay based on infectious HCV pseudoparticles (HCVpp), we have studied the kinetics of humoral responses in a cohort of acute-phase patients infected during a single nosocomial outbreak in a hemodialysis center. The 17 patients were monitored for the spontaneous outcome of HCV infection for 6 months before a treatment decision was made. Blood samples were taken frequently (15 +/- 4 per patient). Phylogenetic analysis of the predominant virus(es) revealed infection by only one of two genotype 1b strains. While all patients seroconverted, their sera induced two opposing effects in HCVpp infection assays: inhibition and facilitation. Furthermore, the ability of sera to facilitate or inhibit infection correlated with the presence of either infecting HCV strain and divided the patients into two groups. In group 1, the progressive emergence of a relatively strong neutralizing response correlated with a fluctuating decrease in high initial viremia, leading to control of viral replication. Patients in group 2 failed to reduce viremia within the acute phase, and no neutralizing responses were detected despite seroconversion. Strikingly, sera of group 2, as well as naive sera, facilitated infection by HCVpp displaying HCV glycoproteins from different genotypes and strains, including those retrieved from patients. These results provide new insights into the mechanisms of viral persistence and immune control of viremia.
authors.affiliation: LVRTG, ENS de Lyon, 46 Allée d'Italie, 69364 Lyon Cedex 07, France.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Lavillette
authors.forename: Yoann
authors.initials: Y
authors.lastname: Morice
authors.forename: Georgios
authors.initials: G
authors.lastname: Germanidis
authors.forename: Peggy
authors.initials: P
authors.lastname: Donot
authors.forename: Alexandre
authors.initials: A
authors.lastname: Soulier
authors.forename: Emanuil
authors.initials: E
authors.lastname: Pagkalos
authors.forename: Georgios
authors.initials: G
authors.lastname: Sakellariou
authors.forename: Liliane
authors.initials: L
authors.lastname: Intrator
authors.forename: Birke
authors.initials: B
authors.lastname: Bartosch
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Pawlotsky
authors.forename: François-Loïc
authors.initials: FL
authors.lastname: Cosset
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000595:Amino Acid Sequence; D015331:Cohort Studies; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000276:immunology*; D006526:Hepatitis C / Q000097:blood* / Q000821:virology*; D018937:Hepatitis C Antibodies / Q000097:blood*; D006801:Humans; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016415:Sequence Alignment; D013997:Time Factors; D014759:Viral Envelope Proteins / Q000235:genetics; D014766:Viremia; D014779:Virus Replication
chemical_list: C087035:E1 protein, Hepatitis C virus; D018937:Hepatitis C Antibodies; D014759:Viral Envelope Proteins; C091015:glycoprotein E2, Hepatitis C virus; D000410:Alanine Transaminase