title: Association of major histocompatibility complex class I haplotypes with disease progression after simian immunodeficiency virus challenge in burmese rhesus macaques.
abstract: Nonhuman primate AIDS models are essential for the analysis of AIDS pathogenesis and the evaluation of vaccine efficacy. Multiple studies on human immunodeficiency virus and simian immunodeficiency virus (SIV) infection have indicated the association of major histocompatibility complex class I (MHC-I) genotypes with rapid or slow AIDS progression. The accumulation of macaque groups that share not only a single MHC-I allele but also an MHC-I haplotype consisting of multiple polymorphic MHC-I loci would greatly contribute to the progress of AIDS research. Here, we investigated SIVmac239 infections in four groups of Burmese rhesus macaques sharing individual MHC-I haplotypes, referred to as A, E, B, and J. Out of 20 macaques belonging to A(+) (n = 6), E(+) (n = 6), B(+) (n = 4), and J(+) (n = 4) groups, 18 showed persistent viremia. Fifteen of them developed AIDS in 0.5 to 4 years, with the remaining three at 1 or 2 years under observation. A(+) animals, including two controllers, showed slower disease progression, whereas J(+) animals exhibited rapid progression. E(+) and B(+) animals showed intermediate plasma viral loads and survival periods. Gag-specific CD8(+) T-cell responses were efficiently induced in A(+) animals, while Nef-specific CD8(+) T-cell responses were in A(+), E(+), and B(+) animals. Multiple comparisons among these groups revealed significant differences in survival periods, peripheral CD4(+) T-cell decline, and SIV-specific CD4(+) T-cell polyfunctionality in the chronic phase. This study indicates the association of MHC-I haplotypes with AIDS progression and presents an AIDS model facilitating the analysis of virus-host immune interaction.
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, Toyama, Shinjuku-ku, Tokyo, Japan.
authors.forename: Takushi
authors.initials: T
authors.lastname: Nomura
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Teiichiro
authors.initials: T
authors.lastname: Shiino
authors.forename: Naofumi
authors.initials: N
authors.lastname: Takahashi
authors.forename: Taku
authors.initials: T
authors.lastname: Nakane
authors.forename: Nami
authors.initials: N
authors.lastname: Iwamoto
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ishii
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Tsukamoto
authors.forename: Miki
authors.initials: M
authors.lastname: Kawada
authors.forename: Saori
authors.initials: S
authors.lastname: Matsuoka
authors.forename: Akiko
authors.initials: A
authors.lastname: Takeda
authors.forename: Kazutaka
authors.initials: K
authors.lastname: Terahara
authors.forename: Yasuko
authors.initials: Y
authors.lastname: Tsunetsugu-Yokota
authors.forename: Naoko
authors.initials: N
authors.lastname: Iwata-Yoshikawa
authors.forename: Hideki
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Tetsutaro
authors.initials: T
authors.lastname: Sata
authors.forename: Taeko K
authors.initials: TK
authors.lastname: Naruse
authors.forename: Akinori
authors.initials: A
authors.lastname: Kimura
authors.forename: Tetsuro
authors.initials: T
authors.lastname: Matano
mesh_terms: D000483:Alleles; D000818:Animals; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology / Q000821:virology; D004195:Disease Models, Animal; D018450:Disease Progression; D015658:HIV Infections / Q000235:genetics* / Q000276:immunology / Q000473:pathology* / Q000821:virology; D015497:HIV-1 / Q000235:genetics / Q000276:immunology; D006239:Haplotypes; D015395:Histocompatibility Antigens Class I / Q000235:genetics* / Q000276:immunology; D006801:Humans; D008253:Macaca mulatta; D016097:Simian Acquired Immunodeficiency Syndrome / Q000235:genetics* / Q000276:immunology / Q000473:pathology* / Q000821:virology; D015302:Simian Immunodeficiency Virus / Q000235:genetics / Q000276:immunology / Q000502:physiology*
chemical_list: D015395:Histocompatibility Antigens Class I