Grant: Operating Grant - PA: HIV/AIDS Research Initiative - Biomedical/Clinical Stream

Our gut normally contains trillions of bacteria that are kept separated from us by a single layer of cells that is the lining of the small and large intestines. These microbes represent a complex ecosystem that is generally beneficial and even essential for our health. Loss of gut-to-blood barrier integrity or disturbances in the composition of the microbe ecosystem has been linked with multiple disorders, ranging from inflammatory bowel disease to obesity and even to anxiety and depression. Early following infection, HIV-1 causes substantial damages to the gut-to-blood barrier by destroying immune cells involved in its maintenance. This results in leakage of gut content and bacterial components in the bloodstream, which triggers inflammation and precipitates AIDS progression. This injury is only partially restored when individuals are treated with antivirals and a chronic low-level inflammation remains which has been associated to higher risks of heart attack and stroke in long-term treated HIV-1 patients. We propose to study the impact of the gut microbiota and its generated products on the biology of HIV-1, more precisely on its ability to infect its main cellular targets, its capacity to replicate in these cells, its capacity to hide from the immune system and its ability to rebound even after many years of effective treatment. These studies will provide fundamental knowledge on the complex relations between gut microbes, the immune system and HIV-1 that could then be exploited to better control this disease or achieve a cure for infected individuals.