AIDSWEEKLY Plus; Monday, May 9, 2005
Staff Medical Writers

According to recently published research from the United States, "Retroviruses encounter dominant postentry restrictions in cells of particular species.

"Human immunodeficiency virus type 1 (HIV-1) is blocked in the cells of Old World monkeys by TRIM5alpha, a tripartite motif (TRIM) protein composed of RING, B-box 2, coiled-coil, and B30.2(SPRY) domains. Rhesus monkey TRIM5alpha (TRIM50alpha(rh)) more potently blocks HIV-1 infection than human TRIM5alpha (TRIM5alpha(hu))."

"Here, by studying chimeric TRIM5alpha proteins, we demonstrate that the major determinant of anti-HIV-1 potency is the B30.2(SPRY) domain. Analysis of species-specific variation in TRIM5alpha has identified three variable regions (v1, v2, and v3) within the B30.2 domain," reported M. Stremlau and colleagues at Harvard University.

"The TRIM5alpha proteins of Old World primates exhibit expansion, duplication, and residue variation specifically in the v1 region. Replacement of three amino acids in the N terminus of the TRIM5alpha(hu) B30.2 v1 region with the corresponding TRIM5alpha(rh) residues resulted in a TRIN15alpha molecule that restricted HIV-1 nearly as efficiently as wild-type TRIM5alpha(rh).

"Surprisingly," continued the authors, "a single-amino-acid change in this region of TRIM5alpha(hu), allowed potent restriction of simian immunodeficiency virus, a phenotype not observed for either wild-type TRIM5alpha(hu) or TRIM5alpha(rh)."

"Some of the chimeric TRIM5alpha proteins that are >98% identical to the human protein yet mediate a strong restriction of HIV-1 infection may have therapeutic utility. These observations implicate the v1 variable region of the B30.2(SPRY) domain in TRIM5alpha(rh) antiviral potency," Stremlau suggested.

Stremlau and colleagues published their study in the Journal of Virology (Species-specific variation in the B30.2(SPRY) domain of TRIM5 alpha determines the potency of human immunodeficiency virus restriction. J Virol. 2005 Mar;79(5):3139-45.

For additional information, contact J. Sodroski, Harvard University, Dana Farber Cancer Institute, School of Medicine, Division AIDS, Department Pathology, Department Cancer Immunology & AIDS, 44 Binney St., JFB 824, Boston, MA 02115, USA.

Publisher contact information for the Journal of Virology is: American Society Microbiology, 1752 N St. NW, Washington, DC 20036-2904, USA.

Keywords: Boston, Massachusetts, United States, AIDS/HIV, B30.2(SPRY) Domain, Viral Pathogenesis, TRIM5alpha, Viral Potency.

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

Reference

Stremlau M, Perron M, Welikala S, et al., Species-specific variation in the B30.2(SPRY) domain of TRIM5alpha determines the potency of human immunodeficiency virus restriction, J Virol. 2005 Mar;79(5):3139-45.

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