Discovery may lead to new HIV drugs, says Jefferson virologist

August 07, 2002

When scientists at London's King's College and their colleagues elsewhere uncovered the identity of a gene that prevents HIV from reproducing, but which is itself blocked by an HIV protein, they took a huge step in solving one of the great puzzles of the virus' biology.

What's more, the discovery, says virologist Roger J. Pomerantz, M.D., "could start a new genre of AIDS drugs."

Researchers found that a gene called CEM15 is a natural inhibitor of HIV, acting as a brake on HIV's development. They showed that biologically tying up a protein called Vif, or Virion infectivity factor, allows CEM15 to stop the virus from replicating.

Vif, then, could become "a new target against which we can develop HIV drugs," says Dr. Pomerantz, professor of medicine, biochemistry and molecular pharmacology and chief of the division of infectious diseases at Jefferson Medical College of Thomas Jefferson University in Philadelphia. His News and Views editorial and commentary accompanies a paper on the finding August 8, 2002 in the journal Nature.

"It's the first regulatory protein against which you might be able to develop an antiviral," says Dr. Pomerantz, who is also director of the Center for Human Virology at Jefferson Medical College.

Scientists have known about Vif since the mid 1980s, Dr. Pomerantz explains. Vif, he says, is a regulatory protein needed for the virus to grow and make infectious viruses, or particles, from certain cells, but not from others. "If researchers tried to grow virus in certain immune system cells, such as peripheral blood T cells, monocyte macrophages and many T cell lines from humans, they needed Vif or the viruses died." That is, the new viruses made by an infected T cell could not infect other cells.

More recently, they concluded that there was some unknown natural cellular defense factor that Vif was subverting.

But the question was, what was it about T cells and some other HIV targets that blocked the virus from replicating, and which Vif somehow neutralized? Now, the discovery of CEM15 solves the mystery. "HIV can't make infectious virus particles from T cells or macrophages without it," he says.

"If you can inhibit Vif, or stop it from inhibiting the CEM15 protein, you have a great antiviral," says Dr. Pomerantz, "Nothing in HIV will be infectious."

Much work lies ahead. Researchers, for example, still don't know exactly how Vif works. But learning how to stymie Vif's activity is crucial to allowing CEM15 to affect HIV. "The next step is to understand how Vif inhibits this cell protein," says Dr. Pomerantz, and what CEM15 normally does.
Contact: Steve Benowitz or
Phyllis Fisher
After Hours: 215/955-6060

Thomas Jefferson University

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