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
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.