Dr. Finkel and colleagues used a genetic-based technique called suppressive subtractive hybridization to identify gene products involved in maintaining cell survival, despite HIV infection. By comparing dying T cells with surviving T cells, the researchers identified proteins that were associated with cell survival.
"Our evidence strongly suggests that a gene called HALP plays a crucial role in protecting HIV-infected cells," said Dr. Finkel. The gene had been discovered previously in humans, she added, but the current research is the first to describe HALP's role in HIV infection. Closely related genes in mice and rats act against apoptosis. By dubbing the gene HALP, which stands for "HIV-associated life preserver," Dr. Finkel emphasized the gene's role in protecting HIV's home in host cells.
Dr. Finkel suggests that if HALP interferes with apoptosis, it may play both helpful and harmful roles. Highly similar genes in rats protect cells when blood circulation is interrupted. HALP may similarly exert a beneficial effect in humans during conditions of oxygen deprivation. However, it may be that HIV shanghais HALP for its own designs by promoting latency, which shields infected T cells from immune system attack, leaving them free to reproduce the virus. "HIV uses host cells as a Trojan horse, a safe haven for the virus to hide until it breaks out of latent infection to destroy other cells," said Dr. Finkel.
Dr. Finkel is pursuing further investigations to establish whether HALP indeed triggers the anti-apoptotic functions she discovered in the current study. By shedding light on additional genetic culprits in HIV infection, her studies may provide clues to new treatments. Future drugs could target the proteins that help HIV survive. Many steps, and years of work, separate this knowledge from the development
Contact: Joey McCool
Children's Hospital of Philadelphia