title: Acute emergence and reversion of influenza A virus quasispecies within CD8+ T cell antigenic peptides.
abstract: Influenza A virus-specific CD8(+) cytotoxic T lymphocytes (CTLs) provide a degree of cross-strain protection that is potentially subverted by mutation. Here we describe the sequential emergence of such variants within CTL epitopes for a persistently infected, immunocompromised infant. Further analysis in immunodeficient and wild-type mice supports the view that CTL escape variants arise frequently in influenza, accumulate with time and revert in the absence of immune pressure under MHCI-mismatched conditions. Viral fitness, the abundance of endogenous CD8(+) T cell responses and T cell receptor repertoire diversity influence the nature of these de novo mutants. Structural characterization of dominant escape variants shows how the peptide-MHCI interaction is modified to affect variant-MHCI stability. The mechanism of influenza virus escape thus looks comparable to that recognized for chronic RNA viruses like HIV and HCV, suggesting that immunocompromised patients with prolonged viral infection could have an important part in the emergence of influenza quasispecies.
authors.affiliation: Department of Microbiology and Immunology, University of Melbourne, Parkville, Victoria 3010, Australia.
authors.forename: Sophie A
authors.initials: SA
authors.lastname: Valkenburg
authors.forename: Sergio
authors.initials: S
authors.lastname: Quiñones-Parra
authors.forename: Stephanie
authors.initials: S
authors.lastname: Gras
authors.forename: Naomi
authors.initials: N
authors.lastname: Komadina
authors.forename: Jodie
authors.initials: J
authors.lastname: McVernon
authors.forename: Zhongfang
authors.initials: Z
authors.lastname: Wang
authors.forename: Hanim
authors.initials: H
authors.lastname: Halim
authors.forename: Pina
authors.initials: P
authors.lastname: Iannello
authors.forename: Catherine
authors.initials: C
authors.lastname: Cole
authors.forename: Karen
authors.initials: K
authors.lastname: Laurie
authors.forename: Anne
authors.initials: A
authors.lastname: Kelso
authors.forename: Jamie
authors.initials: J
authors.lastname: Rossjohn
authors.forename: Peter C
authors.initials: PC
authors.lastname: Doherty
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Turner
authors.forename: Katherine
authors.initials: K
authors.lastname: Kedzierska
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000956:Antigens, Viral / Q000235:genetics / Q000276:immunology*; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology*; D015870:Gene Expression / Q000276:immunology; D015395:Histocompatibility Antigens Class I / Q000235:genetics / Q000276:immunology; D006801:Humans; D057131:Immune Evasion; D016867:Immunocompromised Host; D007223:Infant; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics* / Q000276:immunology; D007251:Influenza, Human / Q000276:immunology* / Q000473:pathology / Q000821:virology; D051379:Mice; D008807:Mice, Inbred BALB C; D008969:Molecular Sequence Data; D009154:Mutation; D010455:Peptides / Q000235:genetics / Q000276:immunology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology* / Q000473:pathology / Q000821:virology
chemical_list: D000956:Antigens, Viral; D018984:Epitopes, T-Lymphocyte; D015395:Histocompatibility Antigens Class I; D010455:Peptides; D011948:Receptors, Antigen, T-Cell