HIV/AIDS Pathogenesis: Tumor susceptibility gene 101 variability associated with HIV disease progression

AIDSWEEKLY Plus; Monday, September 4, 2006
Staff Medical Writers

"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," scientists writing in the Journal of Virology report.

According to A.A. Bashirova and colleagues at the U.S. National Institutes of Health, "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," investigators said.

The authors concluded, "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."

Bashirova and colleagues published their study in the Journal of Virology (Consistent effects of TSG101 genetic variability on multiple outcomes of exposure to human immunodeficiency virus type 1. J Virol. 2006 Jul;80(14):6757-63).

Additional information can be obtained by contacting M. Carrington, National Cancer Institute, SAIC Frederick Inc., Laboratory Genom Divers, Frederick, MD 21702, USA.

The publisher of the Journal of Virology can be contacted at: American Society Microbiology, 1752 N St. NW, Washington, DC 20036-2904, USA.

Keywords: Frederick, Maryland, United States, HIV/AIDS, Disease Progression, Tumor Susceptibility Gene 101, CD4 T Cell Depletion, Viral Load.

This article was prepared by AIDS Weekly editors from staff and other reports.

Reference

Bashirova AA, Bleiber G, Qi Y, et al., “Consistent effects of TSG101 genetic variability on multiple outcomes of exposure to human immunodeficiency virus type 1”, J Virol. 2006 Jul;80(14):6757-63.

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