title: Attenuation of multiple Nef functions in HIV-1 elite controllers.
abstract: BACKGROUND
  Impaired HIV-1 Gag, Pol, and Env function has been described in elite controllers (EC) who spontaneously suppress plasma viremia to < 50 RNA copies/mL; however, activity of the accessory protein Nef remains incompletely characterized. We examined the ability of 91 Nef clones, isolated from plasma of 45 EC and 46 chronic progressors (CP), to down-regulate HLA class I and CD4, up-regulate HLA class II invariant chain (CD74), enhance viral infectivity, and stimulate viral replication in PBMC.
  
  
  RESULTS
  In general, EC Nef clones were functional; however, all five activities were significantly lower in EC compared to CP. Nef clones from HLA-B*57-expressing EC exhibited poorer CD4 down-regulation function compared to those from non-B*57 EC, and the number of EC-specific B*57-associated Nef polymorphisms correlated inversely with 4 of 5 Nef functions in these individuals.
  
  
  CONCLUSIONS
  Results indicate that decreased HIV-1 Nef function, due in part to host immune selection pressures, may be a hallmark of the EC phenotype.
authors.affiliation: Center for AIDS Research, Kumamoto University, 2-2-1 Honjo, Kumamoto 860-0811, Japan.
authors.forename: Philip
authors.initials: P
authors.lastname: Mwimanzi
authors.forename: Tristan J
authors.initials: TJ
authors.lastname: Markle
authors.forename: Eric
authors.initials: E
authors.lastname: Martin
authors.forename: Yoko
authors.initials: Y
authors.lastname: Ogata
authors.forename: Xiaomei T
authors.initials: XT
authors.lastname: Kuang
authors.forename: Michiyo
authors.initials: M
authors.lastname: Tokunaga
authors.forename: Macdonald
authors.initials: M
authors.lastname: Mahiti
authors.forename: Florencia
authors.initials: F
authors.lastname: Pereyra
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miura
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
authors.forename: Zabrina L
authors.initials: ZL
authors.lastname: Brumme
authors.forename: Mark A
authors.initials: MA
authors.lastname: Brockman
authors.forename: Takamasa
authors.initials: T
authors.lastname: Ueno
mesh_terms: D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002478:Cells, Cultured; D015536:Down-Regulation; D015497:HIV-1 / Q000276:immunology / Q000472:pathogenicity* / Q000502:physiology; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D006801:Humans; D011110:Polymorphism, Genetic; D020539:Sequence Analysis, Protein; D014766:Viremia; D014771:Virion / Q000235:genetics / Q000472:pathogenicity; D014779:Virus Replication / Q000235:genetics; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000737:chemistry / Q000235:genetics / Q000502:physiology*
chemical_list: D006680:HLA Antigens; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1