title: HLA-associated viral mutations are common in human immunodeficiency virus type 1 elite controllers.
abstract: Elite controllers (EC) of human immunodeficiency virus type 1 (HIV-1) maintain viremia below the limit of detection without antiretroviral treatment. Virus-specific cytotoxic CD8(+) T lymphocytes are believed to play a crucial role in viral containment, but the degree of immune imprinting and compensatory mutations in EC is unclear. We obtained plasma gag, pol, and nef sequences from HLA-diverse subjects and found that 30 to 40% of the predefined HLA-associated polymorphic sites show evidence of immune selection pressure in EC, compared to approximately 50% of the sites in chronic progressors. These data indicate ongoing viral replication and escape from cytotoxic T lymphocytes are present even in strictly controlled HIV-1 infection.
authors.affiliation: Ragon Institute (formerly Partners AIDS Research Center), Massachusetts General Hospital, Charlestown, Massachusetts 02129, USA. miura523@hotmail.com
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Miura
authors.forename: Chanson J
authors.initials: CJ
authors.lastname: Brumme
authors.forename: Mark A
authors.initials: MA
authors.lastname: Brockman
authors.forename: Zabrina L
authors.initials: ZL
authors.lastname: Brumme
authors.forename: Florencia
authors.initials: F
authors.lastname: Pereyra
authors.forename: Brian L
authors.initials: BL
authors.lastname: Block
authors.forename: Alicja
authors.initials: A
authors.lastname: Trocha
authors.forename: Mina
authors.initials: M
authors.lastname: John
authors.forename: Simon
authors.initials: S
authors.lastname: Mallal
authors.forename: P Richard
authors.initials: PR
authors.lastname: Harrigan
authors.forename: Bruce D
authors.initials: BD
authors.lastname: Walker
mesh_terms: D018984:Epitopes, T-Lymphocyte / Q000235:genetics / Q000276:immunology; D015658:HIV Infections / Q000276:immunology* / Q000821:virology*; D020276:HIV Long-Term Survivors; D015497:HIV-1 / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D020125:Mutation, Missense / Q000276:immunology*; D010949:Plasma / Q000821:virology; D011110:Polymorphism, Genetic; D012641:Selection, Genetic; D019562:Viral Load; D014766:Viremia / Q000276:immunology; D054301:gag Gene Products, Human Immunodeficiency Virus / Q000235:genetics; D054311:nef Gene Products, Human Immunodeficiency Virus / Q000235:genetics; D054302:pol Gene Products, Human Immunodeficiency Virus / Q000235:genetics
chemical_list: D018984:Epitopes, T-Lymphocyte; D054301:gag Gene Products, Human Immunodeficiency Virus; D054311:nef Gene Products, Human Immunodeficiency Virus; C514837:nef protein, Human immunodeficiency virus 1; D054302:pol Gene Products, Human Immunodeficiency Virus