title: Impact of Nef-mediated downregulation of major histocompatibility complex class I on immune response to simian immunodeficiency virus.
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.
authors.affiliation: New England Primate Research Center, One Pine Hill Drive, Box 9102, Southborough, MA 01772-9102, USA.
authors.forename: Tomek
authors.initials: T
authors.lastname: Swigut
authors.forename: Louis
authors.initials: L
authors.lastname: Alexander
authors.forename: Jennifer
authors.initials: J
authors.lastname: Morgan
authors.forename: Jeff
authors.initials: J
authors.lastname: Lifson
authors.forename: Keith G
authors.initials: KG
authors.lastname: Mansfield
authors.forename: Sabine
authors.initials: S
authors.lastname: Lang
authors.forename: R Paul
authors.initials: RP
authors.lastname: Johnson
authors.forename: Jacek
authors.initials: J
authors.lastname: Skowronski
authors.forename: Ronald
authors.initials: R
authors.lastname: Desrosiers
mesh_terms: 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*
chemical_list: D015395:Histocompatibility Antigens Class I; C429284:NEF protein, SIV; D054334:Viral Regulatory and Accessory Proteins