Anti Malaria Gene Confers Higher HIV Risk In People Of African Descent

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Main Category: HIV / AIDS
Also Included In: Infectious Diseases / Bacteria / Viruses;  Genetics
Article Date: 17 Jul 2008 - 13:00 PDT

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US and UK scientists investigating a gene variant that protects people of African descent from a serious type of malaria, have discovered that it may increase their vulnerability to HIV infection by as much as 40 per cent, because of the way it allows the HIV virus to attach to red blood cells.

The study was led by researchers at the The University of Texas Health Science Center at San Antonio, and is published in the 17th July issue of Cell Host and Microbe.

25 million Africans living in Sub-Sahara have HIV, more than any other region in the world. This disproportionate burden cannot be fully explained by social factors such as sexual behaviour, said the researchers.

People of African descent have a variant of the DARC (Duffy antigen receptor for chemokines) gene that may disrupt their body's ability to defend against HIV in the early stages of infection.

The researchers looked at how the DARC gene was expressed in a population of 1,266 HIV-positive members of the US military and 2,000 non- infected healthy people. The receptor controlled by the gene is a molecule that sits on the surface of red blood cells and when expressed, acts as a docking site for Plasmodium vivax, one of the two severe types of malaria parasite.

Africans with the genotype DARC-46C/C (DARC-negative phenotype) are resistant to vivax malaria. Thus the Duffy receptor is not expressed on their red blood cells, denying access to the malaria parasite. But using the military personnel data, the researchers found that in African Americans, having this genotype was also linked to a 40 per cent increase in the odds of acquiring HIV-1.

If extrapolated to Africans, the researchers suggested that this phenomenon could explain 11 per cent of the HIV-1 burden in Africa, because of links to this genotype.

Dr Robin A Weiss, senior lead author of the study who is based at University College London said:

"In sub-Saharan Africa, the vast majority of people do not express Duffy on their red blood cells."

"This is one of the first genetic factors particularly common in Africans that has been shown to confer more susceptibility to HIV," he added.

There is also a curious paradox about this variant. The researchers found that once people with this variant (that did not express Duffy) became infected with HIV, they lived longer than the people who did not have this variant, according to the data from the US military personnel.

Another senior lead author, Dr Matthew of the Infectious Disease Clinical Research Program, Uniformed Services University, in Bethesda, Maryland, said:

"This is a clinical cohort of people who have been followed for nearly 25 years."

"The advantage is we have long-term follow-up, the population is ethnically balanced between European and African Americans, and everyone has had the same employer, health care and HIV medication access," he added.

The researchers were not able to explain exactly how the DARC gene variant allowed HIV-1 access to red blood cells, except to say that it was some kind of complex interaction between levels of the gene-controlled chemokines that pass messages in and out of red blood cells and levels of HIV-1. Chemokines are known to be involved in immune response signalling, such as those that control inflammation.

The researchers concluded that:

"Thus, DARC influences HIV/AIDS susceptibility by mediating trans-infection of HIV-1 and by affecting both chemokine-HIV interactions and chemokine-driven inflammation."

"Duffy Antigen Receptor for Chemokines Mediates trans-Infection of HIV-1 from Red Blood Cells to Target Cells and Affects HIV-AIDS Susceptibility."
Weijing He, Stuart Neil, Hemant Kulkarni, Edward Wright, Brian K. Agan, Vincent C. Marconi, Matthew J. Dolan, Robin A. Weiss, and Sunil K. Ahuja.
Cell Host and Microbe, Vol 4, 52-62, 17 July 2008.

Click here for Abstract.

Sources: journal abstract, University of Texas Health Science Center at San Antonio press statement.

Written by: Catharine Paddock, PhD
Copyright: Medical News Today
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