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HIV Subterfuge Revealed -- Virus Uses Devious Strategy To Undermine Immune System

Date:
October 29, 1997
Source:
National Institute Of Allergy And Infectious Diseases
Summary:
NIAID scientists have found that even when HIV does not enter a cell, proteins in the outer envelope of the virus can bind to a molecule called CCR5 on the cell's surface and initiate a biochemical cascade that sends a signal to the cell's interior. This signalling process may activate the cell, making it more vulnerable to HIV infection.

Researchers at the National Institute of Allergy and Infectious Diseases (NIAID) have discovered a devious strategy used by the human immunodeficiency virus (HIV) to undermine the immunesystem.

The scientists found that even when HIV does not enter a cell, proteins in the outer envelope of the virus can bind to a molecule called CCR5 on the cell's surface and initiate a biochemical cascade that sends a signal to the cell's interior. This signalling process mayactivate the cell, making it more vulnerable to HIV infection. It alsomay cause cells to migrate to sites of HIV replication, thereby increasing their vulnerability to infection. If the cell is already infected with HIV, activation may boost its production of the virus.

Drew Weissman, M.D., Ph.D., formerly of the NIAID Laboratory of Immunoregulation (LIR) and now an assistant professor at the University of Pennsylvania; Ronald L. Rabin, M.D., of the NIAID Laboratory of Clinical Investigation; Anthony S. Fauci, M.D., NIAID director and LIR chief; and their colleagues report the new findings inthe Oct. 30, 1997 issue of the journal Nature.

"These new data add to our understanding of the complex ways HIV causes disease," says Dr. Fauci. "It is a truly formidable foe with many tricks up its sleeve." Adds Dr. Weissman, "Our findings suggest that HIV, even without infecting a cell, canprofoundly influence the disease process by activating cells andinfluencing their movement and aggregation."

HIV generally requires two receptors to enter a target cell: CD4, and either CCR5 or CXCR4, depending on the strain of virus. The strains of HIV most commonly seen early in HIV disease, known as macrophage-tropic (M-tropic) viruses, use CD4 and CCR5 for cellentry. Many strains of the simian immunodeficiency virus (SIV), acousin of HIV that infects non-human primates such as monkeys, also use these receptors for cellular entry.

As described in the Nature report, the researchers found that envelope proteins from four different M-tropic HIV strains and one M-tropic SIV strain induced a signal through CCR5 that caused cells to migrate in culture. In contrast, envelope proteins from other strains of the viruses, known as T-cell tropic (T-tropic) strains, did not causesignalling.

"HIV disease is characterized by persistent immune activation, and envelope protein-mediated signalling through CCR5 may contribute directly or indirectly to this heightened state of activation, with negative consequences for the HIV-infected person," Dr. Faucisays.

Not only are HIV replication and spread more efficient in activated cells, but chronic immune activation during HIV disease may result in a massive stimulation of a person's B cells, impairing the ability of these cells to make antibodies against other pathogens.

Chronic immune activation also can result in a form of cellular suicideknown as apoptosis, and in the increased production of signallingmolecules called cytokines that can themselves increase HIV replication.

Co-authors of Drs. Fauci, Weissman and Rabin include James Arthos, Ph.D., Andrea Rubbert, M.D., Mark Dybul, M.D., Ruth Swofford, Sundararajan Venkatesan, M.D., and Joshua M. Farber, M.D., all of NIAID.

NIAID is a component of the National Institutes of Health (NIH). NIAID conducts and supports research to prevent, diagnose and treat illnesses such as AIDS and other sexually transmitted diseases, malaria, tuberculosis, asthma and allergies. NIH is an agency of the U.S. Department of Health and Human Services.

###

Reference: Weissman D, et al. Macrophage-tropic HIV and SIVenvelope proteins induce a signal through the CCR5 chemokinereceptor. Nature 1997;389:981-5.

Press releases, fact sheets and other NIAID-related materials are available on the Internet via the NIAID home page at http://www.niaid.nih.gov.


Story Source:

The above story is based on materials provided by National Institute Of Allergy And Infectious Diseases. Note: Materials may be edited for content and length.


Cite This Page:

National Institute Of Allergy And Infectious Diseases. "HIV Subterfuge Revealed -- Virus Uses Devious Strategy To Undermine Immune System." ScienceDaily. ScienceDaily, 29 October 1997. <www.sciencedaily.com/releases/1997/10/971029140358.htm>.
National Institute Of Allergy And Infectious Diseases. (1997, October 29). HIV Subterfuge Revealed -- Virus Uses Devious Strategy To Undermine Immune System. ScienceDaily. Retrieved July 23, 2014 from www.sciencedaily.com/releases/1997/10/971029140358.htm
National Institute Of Allergy And Infectious Diseases. "HIV Subterfuge Revealed -- Virus Uses Devious Strategy To Undermine Immune System." ScienceDaily. www.sciencedaily.com/releases/1997/10/971029140358.htm (accessed July 23, 2014).

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