HIV after DARC

A genetic variation that defends against malaria has mixed consequences

Battling malaria for millennia helped Africans build barriers against the parasite that causes it, but that defense has proven to be a double-edged sword for HIV infection.

A genetic variation that prevents a protein called the Duffy antigen from being made in red blood cells defends against malaria. But that defense mechanism increases an individual’s chance of contracting HIV by about 40 percent, an international group of researchers reports in the July 17 Cell Host & Microbe. The genetic variant could account for 2 million to 3 million cases of HIV in Africa, where about 95 percent of the population carries the variant. Once infected, though, people who carry the genetic variant are able to survive longer with the disease.

Compared with people of European heritage, people of African descent tend to do slightly better when infected with HIV, says Vicente Planelles, a molecular virologist at the University of Utah School of Medicine in Salt Lake City. When infected with HIV, people of African heritage don’t progress as quickly to AIDS and tend to live slightly longer.

“The slight advantage of Africans can be explained, at least in part, by this variant of the Duffy antigen,” says Planelles, who was not involved in the new study.

The Duffy antigen receptor for chemokines, or DARC, as the protein is formally known, serves as a target on red blood cells for one type of malaria parasite, called Plasmodium vivax. Over many millions of years of living with malaria, people in Africa developed a genetic variation that prevents red blood cells from making the protein, effectively boarding up the door that the parasite uses to enter the cells.

Previously, scientists had hints that DARC could also be involved in HIV infection. The protein’s normal role is to help maintain levels of chemicals called chemokines in the blood. The chemicals prompt white blood cells to move to the site of an infection and trigger inflammation. Chemokines can also inhibit replication of HIV and other viruses.

Other researchers have shown that HIV can latch onto DARC and use the red blood cell as a hiding place until the virus can transfer to a white blood cell.

Matthew Dolan, an infectious disease expert at the UniformedServicesUniversity in Bethesda, Md., studied more than 3,000 members of the Air Force, including 1,200 who are infected with HIV, to find out which genetic factors might play a role in HIV infection and survival. Dolan found that African-Americans who have HIV are far more likely to carry the variant than African-Americans who are not infected. The variant is virtually absent in European-Americans.

Extrapolated to the African population, the variant could be responsible for about 11 percent, “a sizable minority of cases,” Dolan says.

But the researchers also found that the Duffy antigen gene variant lengthened the amount of time it took for AIDS to develop in people who have extra copies of a chemokine gene. The variant also prolonged life, conferring “well over five to six years of protection,” says Sunil Ahuja of the University of Texas Health Science Center in San Antonio and director of the VeteransAdministrationResearchCenter for AIDS and HIV-1 Infection.

The researchers think that people who lack the Duffy antigen on their red blood cells have low levels of HIV-fighting chemokines, causing them to be infected more easily. Once the people are infected, though, the low chemokine levels are helpful because the people don’t have strong inflammation that could make the disease worse.

But interactions of several genes with environmental and social factors will determine who gets infected and how sick they get, the researchers say.

“If you look at the spread of HIV, a lot of factors go into the bottom line,” Dolan says. “You can’t just pin the tag on one and say it is responsible.”

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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