title: Human leukocyte antigen (HLA) class I down-regulation by human immunodeficiency virus type 1 negative factor (HIV-1 Nef): what might we learn from natural sequence variants?
abstract: HIV-1 causes a chronic infection in humans that is characterized by high plasma viremia, progressive loss of CD4+ T lymphocytes, and severe immunodeficiency resulting in opportunistic disease and AIDS. Viral persistence is mediated in part by the ability of the Nef protein to down-regulate HLA molecules on the infected cell surface, thereby allowing HIV-1 to evade recognition by antiviral CD8+ T lymphocytes. Extensive research has been conducted on Nef to determine protein domains that are required for its immune evasion activities and to identify critical cellular co-factors, and our mechanistic understanding of this process is becoming more complete. This review highlights our current knowledge of Nef-mediated HLA class I down-regulation and places this work in the context of naturally occurring sequence variation in this protein. We argue that efforts to fully understand the critical role of Nef for HIV-1 pathogenesis will require greater analysis of patient-derived sequences to elucidate subtle differences in immune evasion activity that may alter clinical outcome.
authors.affiliation: Department of Molecular Biology and Biochemistry, Simon Fraser University, 8888 University Drive, Burnaby, British Columbia V5A 1S6, Canada. pwimanzi@sfu.ca
authors.forename: Philip
authors.initials: P
authors.lastname: Mwimanzi
authors.forename: Tristan J
authors.initials: TJ
authors.lastname: Markle
authors.forename: Takamasa
authors.initials: T
authors.lastname: Ueno
authors.forename: Mark A
authors.initials: MA
authors.lastname: Brockman
mesh_terms: D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D015536:Down-Regulation; D014644:Genetic Variation; D015497:HIV-1 / Q000472:pathogenicity*; D015395:Histocompatibility Antigens Class I / Q000096:biosynthesis*; D006801:Humans; D057131:Immune Evasion; D037521:Virulence Factors / Q000235:genetics / Q000378:metabolism*; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics / Q000378:metabolism*
chemical_list: D015395:Histocompatibility Antigens Class I; D037521:Virulence Factors; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1