Impact of nef-mediated downregulation of major histocompatibility complex class I on immune response to simian immunodeficiency virus

Tomek Swigut, Louis Alexander, Jennifer Morgan, Jeff Lifson, Keith G. Mansfield, Sabine Lang, R. Paul Johnson, Jacek Skowronski, Ronald Desrosiers

Research output: Contribution to journalArticle

81 Scopus citations

Abstract

Functional activities that have been ascribed to the nef gene product of simian immunodeficiency virus (SIV) and human immunodeficiency virus (HIV) include CD4 downregulation, major histocompatibility complex (MHC) class I downregulation, downregulation of other plasma membrane proteins, and lymphocyte activation. Monkeys were infected experimentally with SIV containing difficult-to-revert mutations in nef that selectively eliminated MHC downregulation but not these other activities. Monkeys infected with these mutant forms of SIV exhibited higher levels of CD8+ T-cell responses 4 to 16 weeks postinfection than seen in monkeys infected with the parental wild-type virus. Furthermore, unusual compensatory mutations appeared by 16 to 32 weeks postinfection which restored some or all of the MHC-downregulating activity. These results indicate that nef does serve to limit the virus-specific CD8 cellular response of the host and that the ability to downregulate MHC class I contributes importantly to the totality of nef function.

Original languageEnglish (US)
Pages (from-to)13335-13344
Number of pages10
JournalJournal of virology
Volume78
Issue number23
DOIs
StatePublished - Dec 2004

ASJC Scopus subject areas

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

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