Genetic Variant Raises HIV Risk

  • Share
  • Read Later
Alexander Joe / AFP / Getty

People sit in the waiting room in an anti-retroviral clinic in Emmaus hospital in Winterton, South Africa.

There's no doubt Africans have borne the brunt of the AIDS epidemic. Now researchers in London and Texas say it may have something to do with a single gene variant that could account for 11%, or about 2.5 million, of Africa's HIV cases.

Published in the journal Cell Host & Microbe, the findings center around one gene variation that blocks a receptor from being expressed on the surface of red blood cells. Scientists had previously studied this genetic variant — found almost exclusively in Africans and their descendants — because it also conferred protection against an early form of malaria. (The malaria parasite needed the receptor to infect blood cells; without the receptor, the parasite starved and died.) More than 90% of sub-Saharan Africans lack the red-blood-cell receptor, along with two-thirds of African-Americans. But the variant that once saved its carriers from one disease now appears to make them more susceptible to another. According to the paper, people with the gene variant were 40% more likely to become infected with HIV than people without it.

This is a finding five years in the making. Virologist Robin Weiss of University College London began to study the relevant receptor in 2003, after seeing earlier research that showed how variation in another gene similarly blocked the receptor that allows HIV to enter white blood cells; far fewer people carry that variant. In the lab, Weiss found that the African-specific receptor, called DARC, or duffy antigen receptor for chemokines, also interacted with HIV: the receptor binds to a wide array of proteins that suppress the virus's replication. Intrigued, but unable to explain why the lack of the receptor increased HIV infection, Weiss teamed up with geneticists at the University of Texas and elsewhere to analyze how the gene variant impacts HIV rates in real populations.

It turned out that among a select cohort of American military personnel who had been followed over decades, the roughly 1,200 carriers of the trait, all of whom were African-American, were 40% more likely after adjustments to be infected with HIV than noncarriers. From that sample, Weiss and his colleagues extrapolated the infection risk attributable to the gene variant in Africa, where a 40% increased susceptibility to infection translates to about 11% of all infections.

Interestingly, among the servicemen who were infected with HIV, those who carried the gene variant lived on average two years longer than noncarriers. "We still can't say exactly why," Weiss says. And though the effect of this gene variant, if confirmed, could help explain a huge number of HIV infections, it still cannot come close to explaining the AIDS burden of Africa. Nearly 70% of all HIV-positive people in the world live in sub-Saharan Africa, and prevalence rates in adults in some African countries top 20%. What's more, the gene variant is most common in West Africa, but HIV-infection rates in that region remain very low compared to those in Eastern and Southern Africa, where the disease has festered longest — and where government and medical officials have often turned a blind eye to risky behaviors in the population.

When asked whether his new findings, if replicated, may help guide current policy, Weiss says, "The straight answer is no. It doesn't really help us think about a vaccine." He adds, "It also doesn't help in other ideas about prevention." Eventually, however, researchers hope to learn how the gene variant slows progression of the AIDS, which may inspire new treatments.

On that front, at least, the British and American researchers may have good company. This week a separate team of researchers at the University of Texas announced they had found what may be the virus's "Achilles' heel" — a stretch of amino acids in the HIV envelope protein, which is necessary for the virus to attach to and infect host cells. Those amino acids, researchers say, could someday be a key therapeutic target and may help change the epidemic's course.