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HIV Risk Increased With Gene Variant in People With African Ancestry

by Rajashri on July 18, 2008 at 3:02 PM
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HIV Risk Increased With Gene Variant in People With African Ancestry

A variant of a gene found only in people of African ancestry increases the chances of becoming infected with the human immunodeficiency virus (HIV-1) by 40 per cent, according to an Indian-origin researcher at South Texas Veterans Health Care System and University of Texas Health Science Center at San Antonio.

Sunil Ahuja, however, also points out that once people are infected, the same variant seems to protect against the progression of the disease, enabling those carrying the infection to live about two years longer.

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"It's well-known that individuals vary in their susceptibility to HIV and that after infection occurs, the disease progresses at variable rates," said Ahuja, whose study has been reported in the journal Cell Host and Microbe, a publication of Cell Press.

"The mystery of variable infection and progression was originally thought to be mainly the result of viral characteristics, but in recent years it has become evident that there is a strong host genetic component," he added.
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According to the researchers, the new discovery is one of few genetic risk factors for HIV found only in people of African descent.

They say that in Africa, where about 90 per cent of all people carry the variant, it may be responsible for 11 percent of the HIV burden there.

The researchers say that the gene in question encodes a protein found mainly at the surface of red blood cells, called Duffy Antigen Receptor for Chemokines (DARC).

They say that the DARC variant, found commonly in people of African ancestry, leaves them without this particular red blood cell receptor.

They highlight the fact that the so-called 'DARC-negative' condition has been well studied because it also confers protection against infection by a malaria parasite known as Plasmodium vivax.

The researchers speculate that this DARC gene variant may have risen to such high frequency as protection against some other, more lethal strain of malaria that existed at some time in the past.

Robin Weiss of University College London said: "The big message of this paper is that something that protected people against malaria in the past is now leaving them more susceptible to HIV."

Matthew Dolan of the Wilford Hall United States Air Force Medical Center and San Antonio Military Medical Center adde: "After thousands of years of adaptation, this Duffy variant rose to high frequency because it helped protect against malaria. Now, with another global pandemic on the scene, this same variant renders people more susceptible to HIV. It shows the complex interplay between historically important diseases and susceptibility in contemporary times."

Previous research had shown that HIV could bind to red blood cells via DARC, and that DARC binds a wide array of inflammatory molecules known as chemokines, including one called CCL5, which is highly effective in suppressing replication of HIV-1.

In the latest research, the experts studied cell culture, and found further evidence that HIV binds to DARC on red cells.

"We started looking at red cells together with HIV and, sure enough, the virus attached. The DARC molecule on red cells in cell culture then transferred the virus to lymphocytes to get infected," Weiss said.

When chemokines were added to the mix, less HIV-1 bound to the red cells, confirming that the virus and chemokines were in competition for the DARC receptor.

"Duffy acts somewhat like a sponge. It binds all these chemokine molecules and that binding also extends to HIV, setting up a triumvirate of interactions between DARC, chemokines and virus," Ahuja said.

The researchers also discovered that the prevalence of the "DARC-negative" variant in African Americans was greater amongst those with HIV than in those without.

While the DARC-negative genotype was associated with an increased risk of acquiring HIV infection, the researchers also observed that people with the variant had a slower disease course.

"The parts of a car that get it into gear are separate from those that get it moving once in gear. A similar analogy applies to HIV; the factors that influence its transmission are not necessarily the same as those that influence disease progression," Ahuja said.

"The results underscore that genetic variants that influence transmission and disease progression can differ in their frequency among different populations, with possible impacts on the heterogeneity of HIV disease burden--not just at the level of individuals but also populations," the researchers concluded.

They may also have implications for evaluating the efficacy of HIV vaccines.

Source: ANI
RAS/K
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