Cell surveillance reveals gene meltdown after HIV invasion

FINDING OUT the battle plan of the enemy invariably puts you at an advantage. Documenting the attack of the HIV virus on immune cells may also help to fight the infection, hope researchers who have recorded the stages of genetic havoc the virus wreaks according to a report in Nature. HIV infects and kills T cells in the blood that normally protect against infection, ultimately wiping out the immune system and leading to AIDS. It does so quickly and ruthlessly, researchers from the University of California in San Diego now show. `HIV packs a punch,' says lead researcher Jacques Corbeil.

After swamping T cells with the virus, Corbeil and his colleagues used gene chips to monitor the activity of nearly 7,000 genes over the subsequent 3 days. "This provided a global survey of the process of infection," he explains.

The virus rapidly shut down T-cell genes: more than 500 genes succumbed within 30 minutes, the group found. HIV hijacks the cell's protein-production machinery for its own devices, launching intense viral replication and ultimately triggering cell death. "It takes over the cell," says Corbeil.

Newly designed bioinformatics software helped the team interpret the wealth of data. Each gene on the chip was associated with keywords describing its function, which were used to find groups of genes in pathways that are targeted by HIV. This revealed that energy-production and DNA-repair pathways were switched off, whereas cellular defence pathways and eventually cell-death genes were activated.

"You get an overview of what's happening," says Gary Nabel, director of the Dale and Betty Bumpers Vaccine Research Center, an AIDS vaccine research centre in Bethesda, Maryland. In contrast, previous studies of the cells' response to HIV focused on individual gene products.

Shortly after HIV infection, many T cells are killed. The exact method by which the virus does this has been an ongoing question. Activation of intrinsic cell-death genes suggests that the cell kills itself in an attempt to limit the spread of the virus.

After the initial drop-off, T-cell numbers stabilize at a level that critically determines how long patients are likely to survive. Current drug treatments target enzymes in the virus to try and slow viral replication.

However, the gene-response profile of besieged cells may identify innate pathways in the host cell that could be boosted to fight infection. "It's the way of the future," says Corbeil.

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Section  : Science & Tech
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