Human Protein Tetherin Disables Production of New Infectious HIV

A human cellular protein known as bone marrow stromal cell antigen-2 (BST02) -- also called tetherin -- can interfere with maturation and release of newly produced HIV viral particles, thereby offering protection against infection of additional cells, according to findings from a Canadian laboratory study reported in the December 2010 Journal of Virology.

Below is the text of a press release describing the research issued by the American Society for Microbiology, which publishes the journal.

Cellular Protein Hobbles HIV-1

A cellular protein called BST-2 had already been known to interfere with the spread of human immunodeficiency virus type 1 (HIV-1), by inhibiting the release of its progeny particles from infected cells. Now a team from McGill University, Montreal, shows that in addition, each progeny virion's ability to cause infection is severely impaired.

"BST-2 may exert a more potent inhibition effect on HIV-1 transmission than previously thought," says coauthor Chen Liang. The research is published in the December Journal of Virology.

BST-2 appears to attenuate infectivity of progeny particles by interfering with their maturation. Normally, during synthesis of new virus particles, a protein called PR55Gag is cleaved into three major structural proteins of HIV. "This cleavage process transforms HIV-1 from an immature and non-infectious virion into a mature and infectious virion," says Chen. The protease inhibitors, drugs given to AIDS patients to contain the disease, block this step. Similarly, BST-2 seems to interfere with this step, because in the study, its presence was associated with accumulation of uncleaved Gag precursor and intermediate products. The mechanism of that interference has yet to be elucidated.

BST-2 (bone marrow stromal cell antigen-2), also known as tetherin, is a cellular protein which has been shown to restrict production of enveloped viruses besides HIV-1, including HIV-2, simian immunodeficiency virus, Kaposi's sarcoma herpes virus, Lassa virus, Marburg virus, and Ebola virus. It interferes with release of new virus particles by anchoring one end of itself in the plasma membrane of the infected cell while the other end becomes inserted into the viral envelope.

Different viruses have evolved various countermeasures. For example, in the case of HIV-1, the viral protein Vpu downregulates BST-2 from the cell surface, removing it from virus budding sites.

"The antiviral function of BST-2 has been extensively studied by a number of groups besides ours," says Chen. "Our hope is that the results of all of these studies can eventually be used to develop a BST-2 based anti-HIV-1 therapy."

Investigator affiliations: McGill AIDS Centre, Lady Davis Institute, Jewish General Hospital, Montreal, Quebec, Canada; Departments of Medicine, Microbiology and Immunology, McGill University, Montreal, Quebec, Canada. 

11/30/10

Reference
J Zhang and C Liang. BST-2 Diminishes HIV-1 Infectivity. Journal of Virology 84(23): 12336-12343 (Abstract). December 2010.

Other Source
American Society for Microbiology. Cellular Protein Hobbles HIV-1. Press release. November 16, 2010