title: Identification of two unique naturally occurring Vpr sequence polymorphisms associated with clinical parameters in HIV-1 chronic infection.
abstract: HIV-1 viral protein R (Vpr) plays important roles in HIV-1 replication. Despite the identification of a number of HLA class I-associated immune escape mutations; it is yet known whether immune-driven Vpr polymorphisms are associated with disease outcome. Hereby, we comprehensively analyzed Vpr sequence polymorphisms and their association with disease outcome and host HLA genotypes, by using plasma viral RNA isolated from 444 HLA-typed, treatment-naïve, chronically HIV-1 infected individuals. Vpr amino acid residues at positions 13, 37, 45, 55, 63, 77, 84, 85, 86, and 93 were significantly associated with patients' plasma viral load and/or CD4 count. Further analysis revealed Ala at position 55 was significantly associated with lower plasma viral load; and Thr at position 63 was significantly associated with lower plasma viral load and higher CD4 count. Also, the number of amino acid residues at the two positions, located in a functionally important α-helical domain, correlated inversely with plasma viral load and positively with CD4 count. Moreover, a phylogenetically corrected method revealed residues at positions 55 and 63 are associated with patients' HLA genotypes. Taken together, our results suggest that Vpr polymorphisms at functionally important and immune-reactive sites may contribute, at least in part, to viral replication and disease outcome in vivo. J. Med. Virol. 89:123-129, 2017. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
authors.forename: Doreen
authors.initials: D
authors.lastname: Kamori
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto, Japan.
authors.forename: Zafrul
authors.initials: Z
authors.lastname: Hasan
authors.affiliation: Department of Biological Sciences, Graduate School of Science, The University of Tokyo, Tokyo, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Ohashi
authors.affiliation: AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan.|Institute of Medical Sciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Ai
authors.initials: A
authors.lastname: Kawana-Tachikawa
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto, Japan.|AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Gatanaga
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto, Japan.|AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oka
authors.affiliation: Center for AIDS Research, Kumamoto University, Kumamoto, Japan. uenotaka@kumamoto-u.ac.jp.|International Research Center for Medical Sciences (IRCMS), Kumamoto University, Kumamoto, Japan. uenotaka@kumamoto-u.ac.jp.
authors.forename: Takamasa
authors.initials: T
authors.lastname: Ueno
mesh_terms: D000328:Adult; D018791:CD4 Lymphocyte Count; D005260:Female; D005838:Genotype; D015658:HIV Infections / Q000473:pathology* / Q000821:virology*; D015497:HIV-1 / Q000145:classification* / Q000235:genetics* / Q000302:isolation & purification; D006680:HLA Antigens / Q000235:genetics; D006801:Humans; D008297:Male; D011110:Polymorphism, Genetic; D016896:Treatment Outcome; D019562:Viral Load; D054325:vpr Gene Products, Human Immunodeficiency Virus / Q000235:genetics*
chemical_list: D006680:HLA Antigens; D054325:vpr Gene Products, Human Immunodeficiency Virus; C514912:vpr protein, Human immunodeficiency virus 1
keywords: CD4 count; HIV-1; HLA; Vpr; plasma viral load; sequence polymorphisms