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
To arrange an interview with Dr. McDermott, or to obtain more
information about this study, contact the NIAID Office of Communications
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: