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Random gene expression may drive HIV into hiding

Random fluctuations in gene expression can influence the fates of cells infected with human immunodeficiency virus (HIV) far more than previously thought, according to new research from Howard Hughes Medical Institute (HHMI) researchers at the University of California, Berkeley. By combining experimental and computational studies of HIV's replication cycle, the researchers found evidence that the virus may become latent in some cells by harnessing the random molecular behavior of the cell.

HIV can hide in cells for years before reappearing to make new virus. Latency is considered one of the biggest reasons why drug therapy fails to eradicate HIV from patients. The new findings, which will be published in the July 29, 2005, issue of the journal Cell, could help scientists design new and more effective treatments to slow or halt the progression of HIV infection.

HIV normally replicates rapidly in the body's white blood cells, but, in some cells, the virus stops replicating and becomes dormant. Researchers have long puzzled over how HIV makes the "decision" to become latent or to keep replicating in a certain cell.

"Most of the other groups studying the molecular mechanisms of HIV latency were coming at it from a deterministic point of view based on the belief that the system can only act in a predetermined way," said lead author Leor Weinberger, who conducted the research as an HHMI predoctoral fellow in the laboratory of HHMI investigator Adam Arkin, in close collaboration with David Schaffer in the University of California at Berkeley Department of Chemical Engineering. But the new results show that "any cell that gets infected can go down one of two paths," Weinberger said.

Weinberger now is a postdoctoral fellow at Princeton University.

Inspired by work that Arkin had done in the 1990s, showing that random fluctuations in viral gene expression can influence latency in a bacterial virus, Weinberger wanted to see if the same pr
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Source:Howard Hughes Medical Institute


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