Natural Protein Prevents HIV from Spreading

Natural Protein Prevents HIV from Spreading
Scientists at the Rockefeller University and the Aaron Diamond AIDS Research Center (ADARC) have discovered a molecule that helps keep particles of mutant HIV strains from spreading. The molecule, termed CD317 or tetherin, is a protein located on the surface of human cells that keeps mutant HIV-1 and other virus particles attached to the cell’s outer membrane, preventing then from ‘floating off’ to infect more cells. Further characterization of this mechanism and the viruses’ counteracting mechanisms may lead to the development of new drugs for the treatment of AIDS and other viral diseases.
Dr. Paul Bieniasz (Credit: Rockefeller University) 
Dr. Paul Bieniasz
(Credit: Rockefeller
University)

Human cells have an antiviral activity that inhibits the release of retrovirus particles (membrane-encapsulated viruses possessing an RNA genome and replicated via a DNA intermediate), and other enveloped virus particles. 

Two years ago, Dr. Paul Bieniasz, Head of the Laboratory of Retrovirology and ADARC scientist, discovered that this inhibitory activity is antagonized by the human immunodeficiency virus (HIV) type-1 viral protein U (Vpu). He found that using their Vpu, normal HIV-1 particles are able to extricate themselves from the sticky cell-membrane surface. The HIV-1 Vpu was found to promote the release of diverse retroviruses from human cells.

Recently, Dr. Bieniasz and his colleagues identified the cellular “glue” that keeps viruses tied to a cell. This antiviral mechanism consists of protein-based tethers, termed ‘tetherins’, which cause retention of fully formed virions (virus particles that exist outside a host cell) on infected cell surfaces.

HIV-1 particles (dark circles) lacking Vpu are unable to release themselves from the surface of their host cell, as tetherin keeps them glued to the surface of the cell’s outer membrane, or causes them to be sucked back in and digested within the cell (Credit:  Rockefeller University). 
HIV-1 particles (dark circles) lacking
Vpu are unable to release themselves
from the surface of their host
cell, as tetherin keeps them glued to
the surface of the cell’s outer membrane,
or causes them to be sucked
back in and digested within the cell
(Credit: Rockefeller University).

In order to identify the cause of cell surface stickiness, Dr. Bieniasz and his team analyzed gene expression and activity across all known human genes, and compared between cells that require Vpu for HIV-1 release and those that do not. Ultimately, they identified CD317, a membrane protein, as tetherin. The researchers demonstrated that CD317 expression correlated with a requirement for Vpu during release of HIV-1 and murine leukemia virus particles. When Vpu was absent but CD317 was expressed, large numbers of virus particles accumulated on the infected cell’s surface, but when CD317 was missing, even the Vpu-deficient viruses were able to extricate from the cell. 

By discovering that the CD317 tetherin inhibits retrovirus release and is antagonized by HIV-1 Vpu, the scientists revealed an anti-virus defense mechanism used by our cells. Dr. Bieniasz’s team is now planning to focus on the scope of tetherin’s antiviral activity, and will try to determine whether there are variations that might confer additional immunity or sensitivity to HIV and other viruses. Virology researchers may also study the ways by which viruses evade the tethering mechanism. 

Dr. Bieniasz notes that if drug researchers are able to interfere with the interaction between tetherin and Vpu, his newly discovered protein may even provide a potential therapeutic target. Inhibition of Vpu function and mobilization of tetherin’s antiviral activity may constitute a potential therapeutic strategy in fighting AIDS and other retroviral diseases. 

Another discovery of human cells’ natural ability to defend themselves against HIV infection, previously covered by TFOT, involves the nuclear proteins XPB and XPD.

Other HIV research projects revealed a protein that promotes virus penetration to white blood cells and the efficacy of combination antiretroviral therapy (cART) in treating AIDS patients.     

More information about the tetherin research is available on this Rockefeller University webpage.

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About the author

Einat Rotman

Eynat has a B.Sc in Biology and an M.Sc in Molecular Microbiology and Biotechnology from Tel-Aviv University. She is currently attending a continuing education program in the Pharma-Job Bio-Medical College towards becoming a clinical research associate.

View all articles by Einat Rotman