Impact of Nef-mediated downregulation of major histocompatibility complex class I on immune response to simian immunodeficiency virus.
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.
Swigut
Tomek
T
New England Primate Research Center, One Pine Hill Drive, Box 9102, Southborough, MA 01772-9102, USA.
Alexander
Louis
L
Morgan
Jennifer
J
Lifson
Jeff
J
Mansfield
Keith G
KG
Lang
Sabine
S
Johnson
R Paul
RP
Skowronski
Jacek
J
Desrosiers
Ronald
R
D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015536:Down-Regulation; D015395:Histocompatibility Antigens Class I / Q000032:analysis*; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000276:immunology; D015302:Simian Immunodeficiency Virus / Q000276:immunology*; D054334:Viral Regulatory and Accessory Proteins / Q000737:chemistry / Q000502:physiology*
D015395:Histocompatibility Antigens Class I; C429284:NEF protein, SIV; D054334:Viral Regulatory and Accessory Proteins