Project 461704

HIV continues to be a worldwide pandemic, with approximately 37 million people living with the disease and roughly one million deaths annually. AIDS results from a progressive impairment of the immune system. Currently, the only effective means of treating HIV-1 involves the use of antiretroviral therapy (ART) regimens that suppress viral replication, preventing AIDS, and thus extend patients' lives. Although ART reduces active viral replication it does not purge cells harboring the HIV reservoir and thus HIV patients must remain on costly lifelong treatment that does not fully restore lifespan or quality of life. Thus, developing new strategies to eliminate the HIV reservoir and cure the infection are a global priority. Our work is focussed on harnessing the effects of soluble antiviral immune mediators called interferon (IFN)-alpha subtypes to better treat viral infections such as HIV. Previously, one of these interferon subtypes, IFN-alpha2, was used to successfully treat Hepatitis C infection. We have found that a different interferon, IFN-alpha14, is significantly more potent than IFN-alpha2 at controlling HIV infection. Despite being most potent at controlling HIV infection, IFN-alpha14 is not naturally produced until very late in disease and in small amounts and thus HIV evades its potent effects during infection. We have found that IFN- alpha14 has an impact on the actions of a specific immune subset called Natural Killer (NK) cells. Natural killer cells are experts at finding and destroying virally infected cells and IFN-alpha14 appears to supercharge this immune subset to do that job better. Our work aims to understand how IFN-alpha14 specifically impacts the function of NK cells and then will use this knowledge to harness these effects and incorporate them into new therapeutic strategies to significantly reduce or even completely eliminate HIV infected cells from the body.