title: Nef-mediated resistance of human immunodeficiency virus type 1 to antiviral cytotoxic T lymphocytes.
abstract: Although Nef has been proposed to effect the escape of human immunodeficiency virus type 1 (HIV-1) from cytotoxic T lymphocytes (CTL) through downmodulation of major histocompatibility complex class I molecules, little direct data have been presented previously to support this hypothesis. By comparing nef-competent and nef-deleted HIV-1 strains in an in vitro coculture system, we demonstrate that the presence of this viral accessory gene leads to impairment of the ability of HIV-1-specific CTL clones to suppress viral replication. Furthermore, inhibition by genetically modified CTL that do not require major histocompatibility complex class I-presented antigen (expressing the CD4 T-cell receptor [TCR] zeta-chain hybrid receptor) is similar for both nef-competent and -deleted strains, indicating that Nef does not impair the effector functions of CTL but acts at the level of TCR triggering. In contrast, we note that another accessory gene, vpr, does not induce resistance of HIV-1 to suppression by CTL clones. We conclude that Nef (and not Vpr) contributes to functional HIV-1 immune evasion and that this effect is mediated by diminished antigen presentation to CTL.
authors.affiliation: Division of Infectious Diseases and AIDS Institute, UCLA Medical Center, Los Angeles, California 90095, USA. oyang@mednet.ucla.edu
authors.forename: Otto O
authors.initials: OO
authors.lastname: Yang
authors.forename: Phuong Thi
authors.initials: PT
authors.lastname: Nguyen
authors.forename: Spyros A
authors.initials: SA
authors.lastname: Kalams
authors.forename: Tanya
authors.initials: T
authors.lastname: Dorfman
authors.forename: Heinrich G
authors.initials: HG
authors.lastname: Göttlinger
authors.forename: Sheila
authors.initials: S
authors.lastname: Stewart
authors.forename: Irvin S Y
authors.initials: IS
authors.lastname: Chen
authors.forename: Steven
authors.initials: S
authors.lastname: Threlkeld
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
mesh_terms: D002478:Cells, Cultured; D015693:Gene Products, nef / Q000235:genetics / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D013601:T-Lymphocytes / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014779:Virus Replication; D054311:nef Gene Products, Human Immunodeficiency Virus
chemical_list: D015693:Gene Products, nef; D054311:nef Gene Products, Human Immunodeficiency Virus