-The Indian Institute of Science (IISc) department of Microbiology and Cell Biology (MCB) and the Centre for Infectious Disease Research (CIDR) researchers and their collaborators from the Bangalore Medical College and Research Institute have identified a key role played by hydrogen sulphide (H2S) gas in suppressing the Human Immunodeficiency Virus (HIV).
Increased H2S was found to have a direct effect on reducing the rate at which the virus multiplies in HIV-infected human immune cells. The finding paves the way for developing a more comprehensive antiretroviral therapy against HIV.
The research results are published in the journal eLife which noted that present state-of-the-art combined antiretroviral therapy (cART) is not a cure for HIV. It can only suppress the virus – cause it to become latent. Unfortunately, in some cases, cART is known to fail even when patients fully follow their drug regimen.
Certain negative effects are also associated with cART, like build-up of toxic molecules leading to ‘oxidative stress’ and loss of function in the mitochondria, the cell’s powerhouse. These effects could lead to inflammation and organ damage. Stopping cART is also not an option because the virus can reactivate, emerge from its latent state in the absence of therapy, stated a communiqué from IISc.
Scientists explored the benefits of H2S presence in HIV-infected cells on both oxidative stress and mitochondrial dysfunction, stated Amit Singh, Associate Professor in MCB/CIDR and corresponding author of this study.
In a previous study, Prof. Singh’s lab developed a tool to measure oxidative stress in cells infected with HIV. In that work, the researchers showed that the chemical agent N-acetylcysteine was able to suppress HIV reactivation from latently infected cells. Since H2S also functions as an antioxidant molecule, the researchers wished to see whether their prior insights on oxidative stress and HIV could be translated to show the contribution of H2S on HIV infection.
As the role of H2S in HIV has not been explored before, the authors had to set experiments up from scratch. “Studying the effects of a gaseous molecule on HIV required us to build and validate new model systems,” said Virender Kumar Pal, a PhD student in MCB and the first author of this study.
“We started with experiments on established cell lines before moving on to cells donated by HIV patients in 2019. Our collaborators in the BMC&RI and Prof Annapurna Vyakarnam’s group at CIDR were of great help. Detecting H2S inside the cells was difficult. Since H2S cannot be detected using conventional biochemical techniques, colorimetric and fluorometric techniques were used,” he added.
The researchers studied the effects of natural generation of H2S in HIV-infected cells and supplemented this with a chemical donor. “We observed a direct effect of H2S on suppressing HIV reactivation and replication along with all its other beneficial effects. Our results suggest that maintenance of HIV latency and reactivation are closely linked to the H2S levels in infected cells,” said Prof. Singh.
This opens the door to supplementing cART with chemical donors of H2S to lock HIV in 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 quickly be repurposed for HIV treatment, Prof Singh said.