Title

Consistent Effects of TSG101 Genetic Variability on Multiple Outcomes of Exposure to Human Immunodeficiency Virus Type 1

Authors

Arman A. Bashirova, National Cancer Institute at Frederick
Gabriela Bleiber, University Hospital of Lausanne - Switzerland
Ying Qi, National Cancer Institute at Frederick
Holli Hutcheson, National Cancer Institute at Frederick
Traci Yamashita, Johns Hopkins School of Hygiene and Public Health
Randall C. Johnson, National Cancer Institute at Frederick
Jie Cheng, National Cancer Institute at Frederick
Galit Alter, Massachusetts General Hospital
James J. Goedert, National Cancer Institute at Bethesda
Susan Buchbinder, San Francisco Department of Public Health
Keith Hoots, University of Texas Health Science Center at Houston
David Vlahov, Johns Hopkins School of Hygiene and Public Health
Margaret May, University of Bristol
Frank Maldarelli, National Cancer Institute at Bethesda
Lisa Jacobson, Johns Hopkins School of Hygiene and Public Health
Stephen J. O'Brien, National Cancer Institute at FrederickFollow
Amalio Telenti, University Hospital of Lausanne - Switzerland
Mary Carrington, National Cancer Institute at Frederick

Document Type

Article

Publication Date

7-15-2006

Publication Title

Journal of Virology

ISSN

0022-538X

Volume

80

Issue/No.

14

First Page

6757

Last Page

6763

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 TSG101 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.

Comments

© 2006, American Society for Microbiology

Additional Comments

NIH contract #: N01-CO-12400

NSUWorks Citation

Bashirova, Arman A.; Gabriela Bleiber; Ying Qi; Holli Hutcheson; Traci Yamashita; Randall C. Johnson; Jie Cheng; Galit Alter; James J. Goedert; Susan Buchbinder; Keith Hoots; David Vlahov; Margaret May; Frank Maldarelli; Lisa Jacobson; Stephen J. O'Brien; Amalio Telenti; and Mary Carrington. 2006. "Consistent Effects of TSG101 Genetic Variability on Multiple Outcomes of Exposure to Human Immunodeficiency Virus Type 1." Journal of Virology 80, (14): 6757-6763. https://nsuworks.nova.edu/cnso_bio_facarticles/203

ORCID ID

0000-0001-7353-8301

ResearcherID

N-1726-2015