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Vpr Gene Linked to HIV Immune Dysfunction

Vpr Gene Linked to HIV Immune Dysfunction

LOS ANGELES-Researchers at the AIDS Institute of UCLA have identified an HIV gene that appears to play a role in HIV immunosuppression by inhibiting reproduction of CD4+ T cells.

The Vpr gene expresses a protein that prevents infected T cells from progressing normally through the cell cycle. Cell growth stops in the G2 phase or early in mitosis. The research showed that expression of the Vpr gene protein is necessary and sufficient to cause the arrest (Journal of Virology 69:6304-6313, 1995).

Study investigator Jeremy B.M. Jowett, PhD, said in an interview that more recent data suggest that these cells probably eventually undergo apoptosis, thus implicating the Vpr gene in the ultimate drastic reduction in CD4 cells seen in late-stage HIV infection.

This model for HIV-induced immune dysfunction opens up possible new avenues of therapy. "At this stage, we don't know how the protein acts," Dr. Jowett said. "It could be binding to another protein or turning on other genes, acting as a transcription enhancer. Once we understand it, we can try to block it, perhaps by blocking receptors or by antisense RNA techniques to inhibit transcription."

Importance to Cancer Research

These findings could also be important in cancer research. In laboratory experiments, he said, the Vpr protein arrested the growth of HeLa human cervical cancer cells, which led to cell death. Dr. Jowett's lab has also shown that the Vpr protein can arrest the growth of p53-deficient retinoblastoma cells.

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