Due to the rapid development of antiretroviral therapy (ART), HIV patients can live longer than before. But even if it is a very effective long-term ART, the HIV virus remains stubbornly incurable, so patients need medication for life. Scientists have been convinced that this is because the HIV virus has created a stubborn virus-infected cell nest that allows HIV to survive indefinitely. A recent study done by researchers at Brigham and Women’s Hospital (BWH) explored how the virus acquired its lair. They found that the cell survival mechanism in infected cells was activated, providing potential targets for the future treatment of HIV. The study was published in Immunity.

 

 

“Our research shows that these HIV-infected cells can upregulate anti-apoptotic molecules to maintain their long-term survival,” said Mathias Lichterfeld, Ph.D., from the Department of Infectious Disease at Brigham and Women’s Hospital (BWH) and the author of the study, “These discoveries will lead us to find ways to reduce these stubborn virus nests.”

 

Working with Dr. Steve Carr’s team at Harvard Broad Institute and scientists at MIT, Lichterfeld, and his colleagues used a quantitative proteomics method based on liquid chromatography-tandem mass spectrometry (LC-MS/MS) to analyze the increase the expression of proteins in HIV-infected cells in detail. They found that both BIRC5 and its partner OX40 are involved in the process of long-term survival of these cells.

 

BIRC5, also known as “survivin,” is a member of a family of proteins involved in cell death. It usually expresses in stem cells at embryonic developmental stages, whereas mature cells do not express it, and tumors are a known exception. Cancer cells usually initiate BIRC5, which is related to chemotherapy resistance. This new study shows that BIRC5 may help HIV-1 to infect cells to escape the cell death process, leading to the persistence of these virus-infected cells after decades of ART.

 

In recent years, there have been several cases which use chemotherapy to reduce HIV levels to undetectable levels, but these patients will eventually return to HIV. This study may now point out a new approach: inhibition of the BIRC5-OX40 pathway may reduce the number of infected cells, which provides a new way to clear these stubborn cells.

 

 

Reference

Hsiao-Hsuan Kuo et al, Anti-apoptotic Protein BIRC5 Maintains Survival of HIV-1-Infected CD4 + T Cells, Immunity (2018). DOI: 10.1016/j.immuni.2018.04.004