Viral Escape by Selection of Cytotoxic T Cellâ Resistant Variants in Influenza a Virus Pneumonia
MetadataShow full item record
AbstractAntigenic variation is a strategy exploited by influenza viruses to promote survival in the face of the host adaptive immune response and constitutes a major obstacle to efficient vaccine development. Thus, variation in the surface glycoproteins hemagglutinin and neuraminidase is reflected by changes in susceptibility to antibody neutralization. This has led to the current view that antibody-mediated selection of influenza A viruses constitutes the basis for annual influenza epidemics and periodic pandemics. However, infection with this virus elicits a vigorous protective CD8+ cytotoxic T lymphocyte (CTL) response, suggesting that CD8+ CTLs might exert selection pressure on the virus. Studies with influenza A virusâ infected transgenic mice bearing a T cell receptor (TCR) specific for viral nucleoprotein reveal that virus reemergence and persistence occurs weeks after the acute infection has apparently been controlled. The persisting virus is no longer recognized by CTLs, indicating that amino acid changes in the major viral nucleoprotein CTL epitope can be rapidly accumulated in vivo. These mutations lead to a total or partial loss of recognition by polyclonal CTLs by affecting presentation of viral peptide by class I major histocompatibility complex (MHC) molecules, or by interfering with TCR recognition of the mutant peptideâ MHC complex. These data illustrate the distinct features of pulmonary immunity in selection of CTL escape variants. The likelihood of emergence and the biological impact of CTL escape variants on the clinical outcome of influenza pneumonia in an immunocompetent host, which is relevant for the design of preventive vaccines against this and other respiratory viral infections, are discussed.
CitationJ Exp Med. 2000 Jun 5; 191(11):1853-1868
- Antigenic drift in the influenza A virus (H3N2) nucleoprotein and escape from recognition by cytotoxic T lymphocytes.
- Authors: Voeten JT, Bestebroer TM, Nieuwkoop NJ, Fouchier RA, Osterhaus AD, Rimmelzwaan GF
- Issue date: 2000 Aug
- Sequence variation in the influenza A virus nucleoprotein associated with escape from cytotoxic T lymphocytes.
- Authors: Rimmelzwaan GF, Boon AC, Voeten JT, Berkhoff EG, Fouchier RA, Osterhaus AD
- Issue date: 2004 Jul
- A mutation in the HLA-B*2705-restricted NP383-391 epitope affects the human influenza A virus-specific cytotoxic T-lymphocyte response in vitro.
- Authors: Berkhoff EG, Boon AC, Nieuwkoop NJ, Fouchier RA, Sintnicolaas K, Osterhaus AD, Rimmelzwaan GF
- Issue date: 2004 May
- Influenza basic polymerase 2 peptides are recognized by influenza nucleoprotein-specific cytotoxic T lymphocytes.
- Authors: Anderson RW, Bennink JR, Yewdell JW, Maloy WL, Coligan JE
- Issue date: 1992 Sep
- Differential processing and presentation of the H-2D(b)-restricted epitope from two different strains of influenza virus nucleoprotein.
- Authors: Potter P, Tourdot S, Blanchard T, Smith GL, Gould KG
- Issue date: 2001 May