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Retrovirus resistance linked to a single gene

Latest update : 2008-09-04

In a study published in the journal Science, American scientists have unveiled new evidence that confirms the link between an immunity gene and the production of neutralizing antibodies that could lead to an HIV vaccine.

The AIDS virus is especially hard to fight because few people develop antibodies to neutralize it, but U.S. researchers said on Thursday they have found an immunity gene that may offer a new way to fight back.

They said the gene Apobec3 helps mice develop antibodies against an HIV-like virus, and they think the same gene in humans could lead to a potent vaccine against the human immunodeficiency virus or HIV.

"This gene is central to HIV biology," Dr. Warner Greene of the Gladstone Institutes at the University of California, San Francisco, said in a telephone interview.

So far, efforts to make a vaccine against HIV have failed.

In humans, HIV devotes one of its 9 genes to disabling Apobec3 proteins, which may help explain why people with HIV rarely make antibodies against the virus, he said.

HIV is a retrovirus, which means it copies bits of its own genetic code into the DNA of the host.

"If we could prevent HIV from destroying this key pivotal host factor, we might allow HIV-infected patients to develop neutralizing antibodies like they do in mice," he said.

"It's a translation from mice to men. That's the challenge now," said Greene, whose study appears in the journal Science.

Green's lab and others have been hunting for the gene in mice that allows them to fight off the Friend virus, a retrovirus similar to HIV.

Working with a team at the National Institute of Allergy and Infectious Diseases, the researchers conducted a series of experiments in which they genetically engineered mice to lack the Apobec3 gene. "Sure enough, when we knocked out the Apobec3 gene, they lost their ability to recover from Friend virus infection," Greene said.

He said the discovery of Apobec3's role in retroviral immunity is exciting because genes in this region are active in people who resist HIV infection, suggesting they are making effective antibodies against the virus.

"Blocking this degradation of Apobec3 is probably the most promising new drug target in HIV biology," Greene said.

Antibodies are key to warding off viral infections, and most vaccines against viral diseases stimulate the body to make antibodies against the target virus.

Greene said efforts at developing an HIV vaccine have largely focused on building up a kind of immune cell called a T-cell to attack the virus.

"Those types of approaches are not proving adequate. We are desperately seeking better approaches to creating neutralizing antibodies," he said, adding, "Maybe this will help us."

The AIDS virus infects an estimated 33 million people globally and has killed about 25 million since the pandemic started in the 1980s.

There is no cure but drugs can suppress the virus and allow patients to lead a near-normal life. Without treatment, the virus destroys the immune system, leaving patients susceptible to infections and cancer.

Date created : 2008-09-04