Viral Escape by Selection of Cytotoxic T Cellâ Resistant Variants in Influenza a Virus Pneumonia

Hdl Handle:
http://hdl.handle.net/10675.2/560
Title:
Viral Escape by Selection of Cytotoxic T Cellâ Resistant Variants in Influenza a Virus Pneumonia
Authors:
Price, Graeme E.; Ou, Rong; Jiang, Hong; Huang, Lei; Moskophidis, Demetrius
Abstract:
Antigenic 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.
Citation:
J Exp Med. 2000 Jun 5; 191(11):1853-1868
Issue Date:
5-Jun-2000
URI:
http://hdl.handle.net/10675.2/560
PubMed ID:
10839802
PubMed Central ID:
PMC2213532
Type:
Article
ISSN:
1540-9538
Appears in Collections:
Institute of Molecular Medicine and Genetics: Faculty Research and Presentations

Full metadata record

DC FieldValue Language
dc.contributor.authorPrice, Graeme E.en_US
dc.contributor.authorOu, Rongen_US
dc.contributor.authorJiang, Hongen_US
dc.contributor.authorHuang, Leien_US
dc.contributor.authorMoskophidis, Demetriusen_US
dc.date.accessioned2012-10-26T16:26:41Z-
dc.date.available2012-10-26T16:26:41Z-
dc.date.issued2000-06-5en_US
dc.identifier.citationJ Exp Med. 2000 Jun 5; 191(11):1853-1868en_US
dc.identifier.issn1540-9538en_US
dc.identifier.pmid10839802en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/560-
dc.description.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.en_US
dc.rights© 2000 The Rockefeller University Pressen_US
dc.subjectOriginal Articleen_US
dc.titleViral Escape by Selection of Cytotoxic T Cellâ Resistant Variants in Influenza a Virus Pneumoniaen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC2213532en_US
dc.contributor.corporatenameInstitute of Molecular Medicine and Genetics-

Related articles on PubMed

All Items in Scholarly Commons are protected by copyright, with all rights reserved, unless otherwise indicated.