How HIV Uses Host Cells as a Trojan Horse

Researchers have identified cellular proteins expressed during HIV infection that enable infected cells to avoid apoptosis, protecting the virus and maintaining the infection within the compromised cells. Their findings were published in the March 2004 issue of the journal AIDS.

The new findings, based on cell studies but not patients, may lead to future treatments that could fully eliminate a patient's HIV infection. Current treatments for HIV and AIDS rely on a combination of drugs called highly active antiretroviral therapy (HAART). Although these drugs drive HIV down to undetectable levels, if the treatment is interrupted, latent infection may surge back.

"Furthermore, HAART does not work for some patients, while other patients are unable to tolerate the treatment's strong side effects,” noted lead author Terri H. Finkel, M.D., Ph.D., chief of rheumatology at The Children's Hospital of Philadelphia (PA, USA; www.chop.edu). "Therefore, we urgently need new treatment approaches, including ways to prevent latent infection.”

The current study builds on prior research by Dr. Finkel, which showed that HIV does not always killed infected immune cells, contrary to popular belief. Instead, it kills bystander cells and somehow prevents at least some infected cells from dying. "HIV works as both a sword and shield,” remarked Dr. Finkel. "It destroys some immune cells, while taking over the genetic machinery of other immune cells and protecting itself within those cells.”

Other research had also demonstrated HIV's ability to remain latent within normal-appearing, infected cells despite antiretroviral therapy. This ability, according to Dr. Finkel, implies that some mechanism is protecting the infected cells from aopotosis.

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. Although the gene had been previously discovered in humans, 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 calling the gene HALP, which stands for "HIV-associated life preserver,” Dr. Finkel stressed the role of the gene in protecting HIV's home in host cells.

If HALP interferes with apoptosis, it may play both helpful and harmful roles, according to Dr. Finkel. 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, HIV may usurp 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,” noted Dr. Finkel.

Dr. Finkel is pursuing further research to establish whether HALP indeed triggers the anti-apoptosis functions she found in the current study. By gathering information on other genetic culprits in HI infection, her studies may provide clues to new treatments. Future drugs could target the proteins that help HIV survive.




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