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Consistent effects of TSG101 genetic variability on multiple outcomes of exposure to human immunodeficiency virus type 1

  1. Author:
    Bashirova, A. A.
    Bleiber, G.
    Qi, Y.
    Hutcheson, H.
    Yamashita, T.
    Johnson, R. C.
    Cheng, J.
    Alter, G.
    Goedert, J. J.
    Buchbinder, S.
    Hoots, K.
    Vlahov, D.
    May, M.
    Maldarelli, F.
    Jacobson, L.
    O'Brien, S. J.
    Telenti, A.
    Carrington, M.

  2. Author Address

    NCI, SAIC Frederick Inc, Lab Genom Divers, Frederick, MD 21702 USA. Univ Lausanne Hosp, Inst Microbiol, Lausanne, Switzerland. Univ Lausanne Hosp, Div Infect Dis, Lausanne, Switzerland. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Massachusetts Gen Hosp, Partners AIDS Res Ctr, Charlestown, MA 02129 USA. NCI, Viral Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ Texas, Hlth Sci Ctr, Gulf States Hemophilia Ctr, Houston, TX USA. Univ Bristol, Dept Social Med, Bristol, Avon, England. NCI, HIV Drug Resistance Program, Bethesda, MD 20892 USA.;Carrington, M, NCI, SAIC Frederick Inc, Lab Genom Divers, Frederick, MD 21702 USA.;carringt@mail.ncifcrf.gov
    1. Year: 2006
    2. Date: Jul
  2. Journal: Journal of Virology
    1. 80
    2. 14
    3. Pages: 6757-6763
  4. Type of Article: Article
  5. ISSN: 0022-538X
  1. Abstract:

    Tumor susceptibility gene 101 (TSG101) encodes a host cellular protein that is appropriated by human immunodeficiency virus type 1 (HIV-1) in the budding process of viral particles from infected cells. Variation in the coding or noncoding regions of the gene could potentially affect the degree of TSG101-mediated release of viral particles. While the coding regions of the gene were found to lack nonsynonymous variants, two polymorphic sites in the TSGI01 5' area were identified that were associated with the rate of AIDS progression among Caucasians. These single-nucleotide polymorphisms (SNPs), located at positions -183 and +181 relative to the translation start, specify three haplotypes termed A, B, and C, which occur at frequencies of 67%, 21%, and 12%, respectively. Haplotype C is associated with relatively rapid AIDS progression, while haplotype B is associated with slower disease progression. Both effects were dominant over the intermediate haplotype A. The haplotypes also demonstrated parallel effects on the rate of CD4 T-cell depletion and viral load increase over time, as well as a possible influence on HIV-1 infection. The data raise the hypothesis that noncoding variation in TSG101 affects the efficiency of TSG101-mediated release of viral particles from infected cells, thereby altering levels of plasma viral load and subsequent disease progression.

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  2. DOI: 10.1128/jvi.00094-06
  3. View record in Web of Science®
  4. WOS: 000238770000004

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