title: Constrained pattern of viral evolution in acute and early HCV infection limits viral plasticity.
abstract: Cellular immune responses during acute Hepatitis C virus (HCV) and HIV infection are a known correlate of infection outcome. Viral adaptation to these responses via mutation(s) within CD8+ T-cell epitopes allows these viruses to subvert host immune control. This study examined HCV evolution in 21 HCV genotype 1-infected subjects to characterise the level of viral adaptation during acute and early HCV infection. Of the total mutations observed 25% were within described CD8+ T-cell epitopes or at viral adaptation sites. Most mutations were maintained into the chronic phase of HCV infection (75%). The lack of reversion of adaptations and high proportion of silent substitutions suggests that HCV has structural and functional limitations that constrain evolution. These results were compared to the pattern of viral evolution observed in 98 subjects during a similar phase in HIV infection from a previous study. In contrast to HCV, evolution during acute HIV infection is marked by high levels of amino acid change relative to silent substitutions, including a higher proportion of adaptations, likely reflecting strong and continued CD8+ T-cell pressure combined with greater plasticity of the virus. Understanding viral escape dynamics for these two viruses is important for effective T cell vaccine design.
authors.affiliation: Centre for Clinical Immunology and Biomedical Statistics, Institute for Immunology & Infectious Diseases, Murdoch University and Royal Perth Hospital, Perth, Australia.
authors.forename: Katja
authors.initials: K
authors.lastname: Pfafferott
authors.forename: Silvana
authors.initials: S
authors.lastname: Gaudieri
authors.forename: Axel
authors.initials: A
authors.lastname: Ulsenheimer
authors.forename: Ian
authors.initials: I
authors.lastname: James
authors.forename: Malte
authors.initials: M
authors.lastname: Heeg
authors.forename: David
authors.initials: D
authors.lastname: Nolan
authors.forename: Mina
authors.initials: M
authors.lastname: John
authors.forename: Andri
authors.initials: A
authors.lastname: Rauch
authors.forename: Simon
authors.initials: S
authors.lastname: Mallal
authors.forename: Andrew
authors.initials: A
authors.lastname: Lucas
authors.forename: Paul
authors.initials: P
authors.lastname: Klenerman
authors.forename: Helmut M
authors.initials: HM
authors.lastname: Diepolder
authors.forename: Michaela
authors.initials: M
authors.lastname: Lucas
mesh_terms: D000208:Acute Disease; D000222:Adaptation, Physiological / Q000235:genetics*; D000483:Alleles; D000939:Epitopes / Q000276:immunology; D019143:Evolution, Molecular; D005838:Genotype; D006680:HLA Antigens / Q000276:immunology; D016174:Hepacivirus / Q000235:genetics* / Q000472:pathogenicity / Q000502:physiology*; D006526:Hepatitis C / Q000175:diagnosis / Q000276:immunology / Q000821:virology*; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000276:immunology / Q000821:virology; D006801:Humans; D009154:Mutation; D011379:Prognosis; D013601:T-Lymphocytes / Q000276:immunology / Q000821:virology
chemical_list: D000939:Epitopes; D006680:HLA Antigens