HIV Digest	HIV Digest Archive

An intracellular protein in Old World primates provides them an innate defense against HIV-1, researchers have recently discovered, a finding possibly opening new avenues to develop antiviral therapies.

The researchers began with a well-known observation: Some species of Old World primates including rhesus monkeys, macaques, mangabeys, baboons and African green monkeys-- seem impervious to HIV, but they are susceptible to the simian version, SIV. However, researchers could infect monkeys with hybrid SIV-HIV viruses, which caused AIDS.

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In asking what made the difference between a virus that could infect monkeys and one that could not, researchers focused on the capsid, a candy-corn shaped casing that surrounds the virus' genes when it enters a cell. Hybrid viruses that could infect monkeys had SIV capsids but HIV genes. Viruses with capsids that were human-monkey mixtures could not infect the monkeys.

Researchers discovered that the monkey's TRIM5-alpha protein blocked HIV as soon as it slipped into cells, preventing the virus from shedding the hard casing around its genes. If the scientists placed the TRIM5-alpha gene into human cells, the human cells made the monkey protein and were protected from HIV. And blocking the TRIM5-alpha gene in monkey cells made the cells susceptible to HIV.

How TRIM5-alpha works is not yet known. The mechanism is independent of the antibodies and white blood cells of the immune system and appears to have evolved to protect animals from specific viruses. The proteins cluster together, drift through cells, and apparently stop viruses when they enter.

While humans make a TRIM5-like protein, it is only half as effective in blocking HIV. And monkey TRIM5 is only about 50 percent effective in blocking SIV. Its big effect is in blocking HIV in monkey cells.

Editor's Note: from the New York Times