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African Gene That protected Against Malaria Increases Risk by 40% for Contracting HIV
 
 
  Wall St Jnl July 17, 2008 By GAUTAM NAIK
 
In that oldest and deadliest of wars, between man and microbe, scientists are starting to unearth clues about a key battleground: the human genome. In an intriguing piece of research, scientists have found that an ancient genetic variation that once protected people of African descent against a certain type of malaria may also make these individuals 40% more susceptible to infection by HIV, the virus that causes AIDS.
 
Factors such as poverty and the number of sex partners are familiar explanations for the disproportionately great toll AIDS has taken on Africa, where some 25 million people are infected with HIV. But the latest findings -- which suggest that both Africans and African-Americans are particularly vulnerable to HIV infection -- indicate that genetics plays a significant role.
 
"Infections have had a big effect of shaping our genome," says Sunil Ahuja, a physician who specializes in infectious disease at the University of Texas Health Science Center at San Antonio and who is a co-author of the paper. By exploiting the malaria-related alteration, he adds, "HIV is using a very creative ploy to advance its pathogenicity."
 
In another twist, the researchers found that the same genetic alteration appears to delay progression to AIDS, prolonging survival in those who are infected with HIV by about two years.
 
The study, which took about five years to put together, was conducted by researchers from several institutions in the U.S. and U.K. It appears in Cell Host and Microbe, a new scientific journal.
 
This particular man-microbe fight has been playing out over tens of thousands of years at an evolutionary pace. Scientists believe that a form of vivax malaria, an ancient relative of the parasite, once swept the African continent and humans there eventually developed the genetic alteration to make them resistant to the disease. Today, vivax malaria is hardly found in Africa.
 
But the change persists in the genome of most Africans -- making them more vulnerable to HIV without protecting them against current forms of malaria. A modern-day malady, HIV, is exploiting that old genetic defense, and apparently using it to infect people more easily. In addition, because HIV-infected people with the variant survive two years longer, they can potentially spread the virus over a longer period of time.
 
Scientists have long been puzzled about how the genetic makeup of a person might influence his or her susceptibility to HIV. One study showed that a small group of prostitutes in Nairobi, Kenya, were more resistant to HIV infection than their fellow prostitutes in the area, even though all engaged in similar high-risk behavior. And only 10% to 30% of children born to HIV-positive mothers are infected by the virus, while the remainder seem to benefit from some form of resistance.
 
The authors of the latest study said there are no immediate practical benefits. In theory, a "susceptibility test" based on the gene variant would be easy to devise, but while a positive reading might spur caution in those with the variant, the test also could persuade those who don't have the genetic trait to pursue riskier behavior and increase their chances of getting infected. Another possible use: vaccine trials, where the genetic makeup of different groups of participants can have a bearing on the results, and allow scientists to tailor the vaccine to the groups most likely to benefit.
 
In their study, the researchers focused on a gene associated with the Duffy protein, found on the surface of red blood cells, which both confers protection against HIV and, experiments suggest, was used by vivax malaria as an entry point into the host's body. People who have the variant gene, which includes many people of African descent, don't carry the Duffy protein.
 
"It helps in part to explain why HIV is so prevalent in Africa," says Robin Weiss, a virologist specializing in HIV at University College London and a co-author of the paper.
 
According to the study, about 90% of people in Africa and some 60% of African-Americans carry the variant gene. In Africa, the scientists estimate, roughly 11% of the HIV burden may be linked to this genetic variation. The study, of about 2,400 U.S. Air Force recruits, was based on data collected over 25 years by the Air Force, and included samples from both African-Americans and those of European descent. Prof. Weiss now plans to do similar research using an even larger group in Africa itself.
 
"We want to see if this really applies to Africa," he says.

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