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NIAID Scientists Discover HIV Disease-Slowing Mutation

Date:
September 24, 1998
Source:
National Institute Of Allergy And Infectious Diseases
Summary:
A common genetic mutation significantly delays the progression of HIV disease, scientists at the National Institute of Allergy and Infectious Diseases (NIAID) have found.

A common genetic mutation significantly delays the progression of HIV disease, scientists at the National Institute of Allergy and Infectious Diseases (NIAID) have found.

Philip M. Murphy, M.D., and David H. McDermott, M.D., of NIAID's Laboratory of Host Defenses, led a research team that screened blood samples from HIV-infected individuals for mutations in the gene for CCR5, a key HIV co-receptor. The CCR5 gene encodes a protein on human immune cells that helps HIV enter and infect those cells. Recent studies have shown that individuals who produce mutant forms of CCR5 protein are more likely to resist HIV infection or have slower HIV disease progression than individuals who produce normal CCR5 protein.

This time, the researchers wanted to see if mutations in the promoter, a region of the CCR5 gene that regulates the quantity, rather than quality, of CCR5 protein, might also influence HIV disease progression. Their suspicions that such mutations would slow disease progression were confirmed. The scientists discovered that individuals with promoter mutations in both of the CCR5 genes they inherited developed AIDS almost four years later, on average, than HIV-infected individuals who lacked the mutation. Laboratory analyses showed that the mutant promoter was 45 percent less active, and thus less effective at promoting CCR5 protein production, than the normal promoter.

Approximately 20 percent of the HIV-infected individuals in the study possessed two copies of the mutant CCR5 promoter. Since the vast majority of these individuals were Caucasians, the researchers screened random blood samples from healthy donors to get an estimate of the promoter mutation's prevalence among the general population. They found two copies of the mutation in 32 percent of African Americans, 28 percent of Asians, 18 percent of Caucasians and 10 percent of Hispanics in the sample.

"This is the first HIV disease-modifying genetic variant found in a regulatory region of the CCR5 gene," notes Dr. McDermott. "It is extremely common, has a broad racial distribution and exerts a strong protective effect against disease progression."

In addition to providing an important new piece to the puzzle of genetic protection against HIV disease, the finding could point to new opportunities in HIV treatment research.

"The information may have a therapeutic application if methods can be developed to block specific regulatory factors at this or other sites that affect CCR5 production."

A report of the study, titled "CCR5 promoter polymorphism affects HIV-1 disease progression," was published in the Sept. 12, 1998, issue of The Lancet.

To arrange an interview with Dr. McDermott, or to obtain more information about this study, contact the NIAID Office of Communications at 301-402-1663.

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

###

For more information on CCR5 and other HIV co-receptors, see the following press releases on the NIAID Web site:

** Sept. 15, 1997, Mutant Gene Not Sole Explanation for HIV Non-Progression

** January 23, 1997, Scientists to Discuss Chemokine Receptor Research

** June 19, 1996, NIAID Researchers Identify Second Fusion Cofactor for HIV

** May 9, 1996, NIAID Researchers Identify Cofactor for Entry of HIV into Cells


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. "NIAID Scientists Discover HIV Disease-Slowing Mutation." ScienceDaily. ScienceDaily, 24 September 1998. <www.sciencedaily.com/releases/1998/09/980923110809.htm>.
National Institute Of Allergy And Infectious Diseases. (1998, September 24). NIAID Scientists Discover HIV Disease-Slowing Mutation. ScienceDaily. Retrieved September 16, 2014 from www.sciencedaily.com/releases/1998/09/980923110809.htm
National Institute Of Allergy And Infectious Diseases. "NIAID Scientists Discover HIV Disease-Slowing Mutation." ScienceDaily. www.sciencedaily.com/releases/1998/09/980923110809.htm (accessed September 16, 2014).

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