Scientists discover new target for HIV drugs

Scientists based in London have discovered a potential target for new anti-HIV drugs that exploits the body’s own defence system against the virus.

With increasing evidence that those infected by HIV are developing resistance to existing drug therapies, the research could mark a major step forward in identifying alternative ways to attack the virus.

“These are very significant findings, and could open the door to new treatments for HIV/AIDS in the future,” says Michael Malim of King’s College London, a member of the research team.

The researchers discovered a gene in human T-cells — those that are infected by HIV — which codes for an enzyme that normally defends cells against the virus. But they also found that HIV can avoid this natural defensive mechanism by producing a protein, known as Vif (virion infectivity factor). This inhibits the so-called CEM15 gene, enabling the virus to live and replicate inside the infected cell.

Making cells ‘Vif-proof’ — by blocking Vif’s inhibition of CEM15 — could therefore be an important way to fight HIV infection in the future.

The Vif protein was first described in the 1980s, and is known to be essential to the survival of HIV; without Vif, the virus is no longer infectious. What was not understood, until know, was exactly how Vif worked.

“Previous studies have shown that Vif is crucial in infection and neutralises some sort of defence system in healthy cells. Our research has identified [the gene] CEM15 as a key component of the system in question,” said Malim.

Malim’s team found that artificially expressing CEM15 in T-cells that normally lack the gene made them more resistant to HIV infection. They believe that this natural defence process could be exploited as a key target for new anti-HIV drugs.

“If we can find a way to block the action of Vif, it would allow CEM15 to work properly and prevent HIV from spreading,” explained Malim.

The researchers believe that the Vif/CEM15 pathway could prove as important as reverse transcriptase and protease, two elements of the HIV lifecycle that are targeted by existing antiviral drugs.

“It’s very ambitious, but we may see Vif [become] a new target for therapy in the next ten years,” Malim concludes.

Link to Nature research paper: ‘Isolation of a human gene that inhibits HIV-1 infection and is supressed by the viral Vif protein’

Reference: Nature Advanced Online Publication (14 July 2002)

© SciDev.Net 2002

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