Is HIV progression sex-linked?

A genetic variant on the X chromosome may explain why some HIV-infected women are slower to develop full-blown AIDS than men. Although several human genetic variants have been implicated in the control and spread of HIV within a host, this is the first time that a sex chromosome has been found to harbor a suspect stretch of genome related to the disease.HIV-1 budding from cultured lymphocyte Image: C. Goldsmith, courtesy of the Centers for Disease Control and Prevention "I think it's a fascinating piece of work," linkurl:Sunil Ahuja,;http://class.ysu.edu/~polisci/ahuja/index.html an infectious disease geneticist at the University of Texas Health Science Center in San Antonio, told __The Scientist__. "It allows us to begin to probe some of those rather tantalizing reports that [HIV-infected] women generally do better than men," added Ahuja, who was not involved with the study. German researchers identified a single-nucleotide polymorphism (SNP) located on the X chromosome of 16, or 17%, of 93 HIV-infected women of European descent, according to research published in this month's linkurl:issue;http://www.cell.com/AJHG/ of __The American Journal of Human Genetics__. HIV infection in most women with the SNP, which is nestled into a highly conserved region between two genes, progressed almost four times slower than it did both in women who lacked the variant and in men, some of whom also carried the SNP. Those women displayed a significantly reduced rate of CD4 cell loss throughout the disease's progression and a lower viral load. Strangely, none of the women had the SNP on both X chromosomes. linkurl:Roman Siddiqui,;http://www.dpz.gwdg.de/index.php?id=478 a geneticist at the Leibniz Institute for Primate Research in Germany and one of the lead authors on the __AJHG__ paper, told __The Scientist__ that finding the SNP on the X chromosome was a complete surprise. "We never expected to find this," he said. Siddiqui and his colleagues first focused on the X chromosomal region after combing the genomes of rhesus macaques infected with SIV (the non-human primate equivalent of HIV) for genetic factors influencing the progression of the disease. Through its microsatellite-based genome-wide association study (GWAS) on the monkeys, the German team keyed in on a locus on the X chromosome located between two genes, one thought to be involved in cell signaling and proliferation, and the other thought to be involved in sperm head cytoskeletal construction. To investigate whether or not the region of the X chromosome was also involved in the progression of HIV in humans, Siddiqui turned to human GWAS data generated by American colleagues at the Center for HIV/AIDS Vaccine Immunology (CHAVI), a sprawling collaboration headquartered at Duke University. That phenotypic and X chromosomal SNP genotype data from 93 HIV-positive women and 210 HIV-positive men led them to the finding that the SNP rs5968255 on the X chromosome of female patients corresponded to slower disease progression. "They have used a very logical and innovative approach by probing non-human primates before moving into humans," said Ahuja. "The rhesus monkey work was something like a magnifying glass," Siddiqui said. "It showed us the region we should look at [in humans]." Because all of the patients contained in the CHAVI data were Americans of European decent, Siddiqui decided to comb through the wider HapMap database for the SNP's prevalence in people of other ethnicities. He found that the SNP was four or five times more common in Asian females from Japan or mainland China compared to women of European or African descent. Siddiqui and his team also noted that there were Japanese and Chinese women in the HapMap database that did carry the SNP on both X chromosomes. "[The SNP] is very, very rare among African women," he added. "I think that now we have a clear genetic aspect that must be looked at in the future," Siddiqui said. He is planning a project that involves screening Asian women infected with HIV for the SNP, as well as searching for other genetic host factors lurking in the sex chromosomes that may affect HIV infection and progression. "I'm pretty sure that there are more sex-specific genetic variations which need to now be found." **__Related stories:__***linkurl:Chimps get AIDS too;http://www.the-scientist.com/blog/display/55831/ [22nd July 2009]*linkurl:A new path for HIV entry;http://www.the-scientist.com/blog/display/55670/ [30th April 2009]*linkurl:New hope for HIV microbicide;http://www.the-scientist.com/blog/display/55487/ [4th March 2009]

Is HIV progression sex-linked?

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