More than 50 percent of new HIV infections occurring in the United States each year are among men who have sex with men (MSM). Consequently, the majority of new HIV infections in the country are acquired through rectal transmission. But the role a person’s gut microbiota plays in making them more or possibly less susceptible to rectal acquisition of HIV has not been determined. Angela Wahl, PhD, Research Assistant Professor of Medicine, recently received a multi-million dollar, five-year R01 award from the National Institutes of Health (NIH) for her proposal “The Role of Human Gut Microbiota in HIV-1 Rectal Acquisition, Replication and Pathogenesis.”
“For a young investigator, receiving your first R01 is a big milestone,” says Wahl. “This is an important project because we know the microbiota in the gut influences the immune system, and we know the microbiota in the gut differs for people living with HIV and those who are not. But we do not know how the gut microbiota in a person modulates his or her susceptibility to HIV acquisition.”
The role of gut microbiota in rectal HIV acquisition is not known due to the unavailability of a model system in which the gut microbiota can be selectively colonized, manipulated and analyzed prior to HIV exposure, Wahl says. Past human studies were limited to observations and analyses of feces and biopsied tissue obtained from uninfected and HIV-infected individuals.
Working with partners at UNC and at Rush University and the University of Illinois at Chicago, Wahl’s study will utilize a novel humanized mouse model that is colonized with human gut microbiota originally developed in collaboration with Morgan Chateau, PhD, a former UNC graduate student to establish the role of human gut flora in rectal HIV acquisition, replication, and pathogenesis.
“We will look at the gut microbiome before infection to see if it impacts the number of cells HIV would target during rectal acquisition. We will also study the microbiota after infection to see if it effects HIV replication and pathogenesis,” Wahl says. “We want to know if the composition of your gut microbiota increases or decreases your risk of acquiring HIV, if it changes the course of HIV infection and if it affects the course of disease upon infection.”
Wahl says she is hopeful her study’s results will inform future clinical interventions aimed at preventing rectal HIV transmission. J. Victor Garcia, PhD, Professor of Medicine and an expert on in vivo models for HIV research says that “this is a terrific accomplishment by one of our best young investigators. Dr. Wahl’s experiments will likely shed new light into aspects of fundamental importance regarding the interactions between the microbiome, HIV and the host.”