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Gene helps people resist AIDS infection
A gene that may help block the AIDS virus from getting into cells seems to protect some people from the deadly and incurable infection, researchers said on Thursday.
They found that people who carry extra copies of the gene are less likely to become infected with the virus, which affects 40 million people worldwide.
The findings may eventually lead to better ways to prevent and treat HIV, which has killed more than 25 million people since it was first identified in the early 1980s, said the National Institute of Allergy and Infectious Diseases, which funded the study.
It also may help explain overall human immunity against infectious diseases, the researchers write in an advance report in the journal Science.
The gene, called CCL3L1, controls production of an immune system signaling chemical, or chemokine.
Normally, genetic variation means people have slight mutations or variations in a gene, or working and non-working copies -- one copy inherited from the mother and one from the father. In this case, people actually have multiple copies of the entire gene, said Dr. Sunil Ahuja of the University of Texas Health Science Center in San Antonio, who led the study.
"About five percent of the human genome has got large chunks of sequence that are duplicated," Ahuja said in a telephone interview.
For CCL3L1, some people have no copies of the gene at all and some people have four, five and more. This chemokine is associated with a receptor -- a cellular entryway -- known as CCR5.
CCR5 is known to affect susceptibility to HIV infection and to how quickly an infected person progresses to AIDS.
STUDYING DIFFERENT ETHNIC GROUPS
For their study Ahuja and colleagues in the United States, Britain and Argentina analyzed blood samples from more than 4,300 HIV-infected and non-infected people of different ancestral origins.
They counted how many copies of the CCL3L1 gene each person had, and found big variations.
For example, HIV-negative black adults had an average of four copies of CCL3L1, while HIV-negative European-Americans averaged two copies each and uninfected Hispanic-Americans had an average of three copies.
The more copies a person had, the less likely he or she was to be infected with HIV.
And it was not the absolute number of extra copies of the gene that mattered, Ahuja's team found. Instead, it was whether a person had more copies than average for his or her ethnic group.
In general, each extra copy of the CCL3L1 offered 4 percent to 10 percent protection from the virus, Ahuja said.
About 1 percent of people of Caucasian descent have a mutation in the CCR5 gene that makes them very unlikely to acquire HIV, or to come down with AIDS once infected. That led Ahuja's team to look at chemokines that interact with CCR5.
He described infection as a battle between the virus and the body's immune system chemokines, all trying to get into immune cells called T-cells. "The virus is trying to compete with sites for chemokines," he said. The outcome depends on how much virus is in the blood, how many CCR5 receptors a cell has and how much chemokine is around. Dr. Matthew Dolan, an Air Force colonel at Brooks City-Base in San Antonio who worked on the study, said the finding could help doctors decide when and how to treat HIV-infected patients with cocktails of anti-viral drugs. It could also help in designing new vaccines and testing current HIV vaccines, Dolan said. He said it was unclear if the CCL3L1 chemokine itself could be made into a treatment of vaccine. "You don't know if varying what nature has wrought here could improve this disease or worsen some other disease," Dolan said.
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