Nonsense mutations in the vpr gene of HIV‐1 during in vitro virus passage and in HIV‐1 carrier‐derived peripheral blood mononuclear cells

FEBS Letters

Kurata, Takeshi¹  Fujinaga, Koh⁴  Oka, Shinichi³  Ikuta, Kazuyoshi⁴  Nakaya, Takaaki⁴  Kishi, Masahiko⁴  Jones, Ian M.² 

[1] National Institute of Health, Shinjuku-ku, Tokyo 162, Japan;NERC Institute of Virology, Mansfield Road, Oxford, OX1 3SR, UK;University of Tokyo, Minato-ku, Tokyo 108, Japan;Section of Serology, Institute of Immunological Science, Hokkaido University, Kita-ku, Sapporo 060, Japan

关键词: HIV-1;    Accessory gene;    vpr;    Persistent infection;    Mutation;    HIV-1;    human immunodeficiency virus type 1;    AIDS acquired immune deficiency syndrome;    PCR;    polymerase chain reaction;    PBMC;    peripheral blood lymphocytes;    SIV;    simian immunodeficiency virus;   

DOI  :  10.1016/0014-5793(94)01074-9

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Long-term, persistent infection by HIV-1 is a prerequisite for the development of AIDS. However, little is known of the determinants required for HIV-1 to cause persistence. We have reported previously that persistent infection of a T cell line by a cytopathogenic strain of HIV-1 became increasingly likely with in vitro serial passage of the virus. DNA sequencing of the persistent strains revealed a nonsense mutation in the vpr gene in all isolates tested. Here, we report the development and use of a semi-quantitative PCR method to detect the vpr nonsense mutation within populations of virus. Our results show that vpr mutants also arise in cells during acute infection and increase progressively with serial passage of the virus. In addition, HIV-1-seropositive individuals were examined and found to carry the same vpr nonsense mutation at high frequency in virus-infected PBMC. These data are consistent with a mechanism of HIV-1 persistence in vivo and in vitro in which virus cytopathogenic potential is lost by the build up of nonsense mutations in vpr.

【 授权许可】

Unknown