Miller School Researchers Create Self-Activating AIDS Virus as Novel HIV Vaccine Strategy
HIV, the virus that causes AIDS, does not fully activate key immune cells, according to research led by Geoffrey Stone, Ph.D., research assistant professor of microbiology and immunology at the Miller School. The research findings are available online and published in the August 2011 issue of the Journal of Leukocyte Biology.
Dr. Stone and research fellow Sachin Gupta, Ph.D., inserted the Epstein Barr Virus gene LMP1 into the HIV genome and discovered that it increased immune activation and secretion of inflammatory cytokines.
“When LMP1 was expressed from the HIV genome, suddenly we observed a rapid increase in cytokines and markers of activation with infected macrophages and dendritic cells,” said Dr. Gupta.
The immune cells are natural targets for the virus and also are known to induce chronic inflammation in HIV infected individuals. This research suggests that inflammation may not result from direct HIV infection at all.
“A number of other factors may be more important for chronic inflammation, including ‘leaky gut,’ which results from the destruction of intestinal immune cells during the early stages of HIV infection,” said Dr. Stone. “‘Leaky gut’ leads to high levels of bacterial endotoxins in the blood, which, rather than direct HIV infection of macrophages and dendritic cells, may account for the chronic inflammation we observe in HIV patients.”
The duo also conducted research in which LMP1 was inserted into the SIV genome, a non-human primate version of HIV. The findings, which were published in the May 2011 issue of Retrovirology, suggested that direct activation of HIV infected macrophages and dendritic cells may actually improve immune control of the virus, rather than cause immune dysregulation and chronic inflammation.
These discoveries could play a vital role in the design of novel HIV vaccines and radically change how we view HIV-induced inflammation.