title: Selective downmodulation of HLA-A and -B by Nef alleles from different groups of primate lentiviruses.
abstract: It has been demonstrated that the HIV-1 NL4-3 and IIIB Nef alleles downregulate HLA-A and -B but not -C or -E from the cell surface. It remained elusive, however, whether selective modulation of specific HLA molecules is conserved between different groups of human and simian immunodeficiency viruses, respectively. To address this, we analyzed a large panel of primate lentiviral Nef proteins and we found that this property is conserved among nef alleles from the M, N and O groups of HIV-1, as well as those from SIVcpz, the precursor of HIV-1, and a variety of other highly divergent primate lentiviruses. In conclusion, our data indicate that Nef's ability to selectively downregulate HLA-A and -B alleles to prevent CTL lysis and NK killing of virally infected cells is conserved among different primate lentiviral lineages and preceded the zoonotic transmission of SIVcpz from chimpanzees to humans.
authors.affiliation: Institute of Virology, Universitätsklinikum, 89081 Ulm, Germany.
authors.forename: Anke
authors.initials: A
authors.lastname: Specht
authors.forename: M Quinn
authors.initials: MQ
authors.lastname: DeGottardi
authors.forename: Michael
authors.initials: M
authors.lastname: Schindler
authors.forename: Beatrice
authors.initials: B
authors.lastname: Hahn
authors.forename: David T
authors.initials: DT
authors.lastname: Evans
authors.forename: Frank
authors.initials: F
authors.lastname: Kirchhoff
mesh_terms: D000483:Alleles; D000595:Amino Acid Sequence; D000818:Animals; D016827:CD8 Antigens / Q000378:metabolism; D002460:Cell Line; D015536:Down-Regulation; D015693:Gene Products, nef / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015497:HIV-1 / Q000378:metabolism; D015234:HLA-A Antigens / Q000737:chemistry / Q000378:metabolism*; D015235:HLA-B Antigens / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D019169:Jurkat Cells; D007694:Killer Cells, Natural / Q000276:immunology; D017958:Lentiviruses, Primate / Q000145:classification / Q000378:metabolism*; D008969:Molecular Sequence Data; D015302:Simian Immunodeficiency Virus / Q000378:metabolism; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014162:Transfection
chemical_list: D016827:CD8 Antigens; D015693:Gene Products, nef; D015234:HLA-A Antigens; D015235:HLA-B Antigens