Mutant Gene Blocks HIV's Entry Into Cells
An inherited gene mutation appears to protect some people from infection with the AIDS virus, NIAID-funded researchers have found. Richard A. Koup, M.D., Nathaniel R. Landau, M.D., and their colleagues at the Aaron Diamond AIDS Research Center in New York identified the mutation in two men who remained uninfected despite histories of multiple high-risk sexual exposures to HIV. They reported their findings in the Aug. 9, 1996 issue of the journal Cell.
In laboratory experiments, the researchers were unable to infect the men's T cells with HIV. Genetic analyses indicated that both individuals had identical mutations of the gene encoding CKR-5, a recently discovered "co-receptor" for HIV, that allows the virus to fuse with membranes of CD4+ T cells (see AIDS Agenda, June 1996). The mutant gene produces a dysfunctional form of CKR-5 that does not allow this essential step in the HIV life cycle to occur.
These findings," the authors conclude, "highlight the importance of developing therapeutic agents directed against the HIV-1-CKR-5 interaction."
By analyzing DNA from a random sample of unrelated individuals, the scientists determined that about 1 percent of persons of western European descent carry two copies of the mutant gene, as do the individuals in the study. Approximately 20 percent of people in this population have a single copy of the defective gene. The authors note that it will be important to determine whether such individuals who become infected with HIV progress to disease more slowly than persons who have two good copies of the CKR-5 gene. They speculate that decreased levels of functional CKR-5 may be responsible for the low viral burdens that have been reported in HIV-infected individuals who remain asymptomatic for long periods.