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

Swigut, T., Alexander, L., Morgan, J., Lifson, J., Mansfield, K. G., Lang, S., Johnson, R. P., Skowronski, J., Desrosiers, R. (December 2004) Impact of nef-mediated downregulation of major histocompatibility complex class I on immune response to simian immunodeficiency virus. Journal of Virology, 78 (23). pp. 13335-13344. ISSN 0022-538X

URL: http://jvi.asm.org/content/78/23/13335.full
DOI: 10.1128/​JVI.78.23.13335-13344.2004

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-down regulating 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.

Item Type: Paper
Uncontrolled Keywords: T-CELL-ACTIVATION T-cell activation POLYMERASE CHAIN-REACTION polymerase chain reaction RHESUS-MONKEYS rhesus monkeys ZETA-CHAIN zeta chain LYMPHOCYTE-ACTIVATION lymphocyte activation SURFACE EXPRESSION surface expression CD4 ENDOCYTOSIS endocytosis HIV-1 INDUCTION induction SIV TYPE-1
Subjects: diseases & disorders > viral diseases > HIV
diseases & disorders > viral diseases > SIV
diseases & disorders > viral diseases
CSHL Authors:
Depositing User: CSHL Librarian
Date: December 2004
Date Deposited: 25 Jan 2012 16:03
Last Modified: 25 Jan 2012 16:03
URI: http://repository.cshl.edu/id/eprint/22497

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