The results, researchers say, pave the way for the development of a more comprehensive antiretroviral treatment for HIV. The team included researchers from the Department of Microbiology and Cell Biology (MCB) and the Center for Infectious Disease Research (CIDR) at IISc and people from Bangalore Medical College and Research Institute (BMCRI).
The results have been published in the journal eLife, IISc said in a statement. Pointing out that the current advanced combination antiretroviral therapy (cART) is not a cure for HIV, researchers said it can only suppress the virus – make it latent.
“… Unfortunately, in some cases cART is known to fail, even when patients fully follow the drug regimen. Certain adverse effects are also associated with cART, such as the building up of toxic molecules that lead to ‘oxidative stress’ and loss of function in the mitochondria, the cell’s power center. These effects can contribute to inflammation and organ damage. Stopping cART is also not an option because the virus can be reactivated, “said researchers.
Amit Singh, associate professor, MCB / CIDR and similar author, said researchers have recently begun exploring the beneficial effects of H2S presence in HIV-infected cells on both oxidative stress and mitochondrial dysfunction. The IISc added that in the previous study, Singh’s laboratory developed a tool to measure oxidative stress in cells infected with HIV.
“In that work, we showed that the chemical agent (N-acetylcysteine) could suppress HIV reactivation from latently infected cells. A German study later showed that N-acetylcysteine partially acts by releasing H2S molecules, which was when we began investigating its role, “Singh said.
Previous work from Singh’s laboratory also looked at the effects of counteracting the oxidative stress of an antioxidant nanozyme during HIV infection. “Since H2S also acts as an antioxidant molecule, we wanted to see if our previous insights could be translated to show contributions from H2S to HIV infection,” Singh said.
Given that the role of H2S in HIV has not been studied before, researchers set up experiments from scratch. “Studying the effects of a gaseous molecule on HIV required the construction and validation of new model systems,” said Virender Kumar Pal, the first author of this study.
He said the team started with experiments on established cell lines before moving on to cells donated by HIV patients in 2019, adding that BMCRI collaborators and Prof Annapurna Vyakarnam’s group at CIDR were of great help.
“Detecting H2S inside cells was not a straightforward task. Since H2S cannot be detected using conventional biochemical techniques, we used colorimetric and fluorometric techniques, ”he recalls.
Researchers investigated the effects of natural generation of H2S in HIV-infected cells and supplemented this with a chemical donor. “We observed the direct effect of H2S on suppressing HIV reactivation and replication, along with all its other beneficial effects, such as maintaining mitochondrial health and spreading oxidative stress in cellular models. Our results suggest that maintaining HIV latency and reactivation is closely linked to H2S levels in infected cells, “Singh said.
This, he added, opens the door to supplement cART with chemical donors of H2S to lock HIV into a state of deep latency, potentially improving the lives of millions infected with the virus. “Since H2S donors are already undergoing clinical trials for other diseases, they can be quickly reused for HIV treatment,” he said.