Gladstone Institute researchers provide insight in fight against HIV/AIDS

Warner C. Green and a team of scientists of the Gladstone Institutes published two HIV/AIDS studies in the Nature and Science journal on December 19.

The first study revealed how the HIV virus kills the immune system's CD4 T cells and compromises the immune system. The second study revealed the results of a Phase I clinical study of an anti-inflammatory drug in preventing the HIV virus from killing CD4 T cells.

"Gladstone has made two important discoveries, first by showing how the body's own immune response to HIV causes CD4 T cell death via a pathway triggering inflammation, and secondly by identifying the host DNA sensor that detects the viral DNA and triggers this death response," Robert F. Siliciano, a professor of medicine at Johns Hopkins University and a Howard Hughes Medical Institute investigator, said. "This one-two punch of discoveries underscores the critical value of basic science -- by uncovering the major cause of CD4 T cell depletion in AIDS, Dr. Greene's lab has been able to identify a potential new therapy for blocking the disease's progression and improving on current antiretroviral medications."

The first study found that the HIV virus succeeds in compromising the body's immune system when the CD4 T cells become infected with the virus and self-destruct in an attempt to protect the body from the spread of infection. This, instead, leads to the failure of the immune system, as remnants of the HIV virus are still present and attract more cells to initiate the death cycle. The study provided researchers with insight into what type of vaccine is needed to potentially prevent infection.

The second study found that an existing anti-inflammatory drug reduces the function of the IFI16 protein, inhibiting pyroptosis and potentially the death cycle in the body. The research team, which also includes Kathryn M. Monroe and Zhiyuan Yang of Gladstone, plans to conduct a Phase II trial in the near future, which will look at the drug's ability to block pyroptosis in HIV-positive patients.

"This has been an absolutely fascinating voyage of discovery," Greene said. "Every time we turned over an 'experimental rock' in the studies, a new surprise jumped out."