Vpr Gene Linked to HIV Immune Dysfunction

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

The Vpr gene expresses a protein that prevents infected T cellsfrom progressing normally through the cell cycle. Cell growthstops in the G2 phase or early in mitosis. The research showedthat expression of the Vpr gene protein is necessary and sufficientto cause the arrest (Journal of Virology 69:6304-6313, 1995).

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

This model for HIV-induced immune dysfunction opens up possiblenew avenues of therapy. "At this stage, we don't know howthe protein acts," Dr. Jowett said. "It could be bindingto another protein or turning on other genes, acting as a transcriptionenhancer. Once we understand it, we can try to block it, perhapsby blocking receptors or by antisense RNA techniques to inhibittranscription."

Importance to Cancer Research

These findings could also be important in cancer research. Inlaboratory experiments, he said, the Vpr protein arrested thegrowth of HeLa human cervical cancer cells, which led to celldeath. Dr. Jowett's lab has also shown that the Vpr protein canarrest the growth of p53-deficient retinoblastoma cells.