Angela Wahl, PhD, an assistant professor in the Division of Infectious Diseases in the Department of Medicine, and a member of the Institute for Global Health & Infectious Diseases (IGHID), has received a $3.2 million R01 award to study the role of microglia in HIV latency and persistence in the brain.
Over 38 million people are living with HIV worldwide. While the once life-threatening brain complications associated with HIV infection are now relatively uncommon in people living with HIV (PLWH), due to the availability of highly effective antiretroviral therapy (ART), up to 50% of PLWH still experience HIV-associated neurological disorders (HAND). Age-associated cognitive decline is also exacerbated in PLWH. The continued high prevalence of HAND in PLWH suggests the persistence of HIV infected cells in the brain.
Microglia, long-lived immune cells in the brain, are a major target of HIV infection in the central nervous system and thought to represent the main cell reservoir of HIV in brain of PLWH. While the concept of microglia cells as HIV reservoirs has long been recognized, it is nearly impossible to study the brain tissue of living people with HIV.
As principal investigator of the five-year award from the NIH National Institute of Mental Health (NIMH), Dr. Wahl will lead an investigative team, with fellow UNC faculty Nancie Archin, PhD, assistant professor in infectious diseases and IGHID member, Guochun Jiang, PhD, assistant professor of biochemistry and biophysics, Corbin Jones, PhD, professor of biology and genetics, and collaborators from Virginia Commonwealth, Harvard, and the University of Nebraska, to utilize an innovative precision animal model reconstituted with human brain microglia, to study how these cells contribute to HIV latency, persistence and viral rebound.
“We are excited to launch this multidisciplinary study to answer questions that we have never been able to assess before,” said Wahl. “Until recently, it wasn’t possible to study HIV infection of human microglia in an in vivo system. We will be able to investigate the role of these cells during the establishment of HIV infection in the brain, determine their location, and understand HIV persistence under therapy and reactivation, all of which will aid the development of novel HIV cure approaches that target the central nervous system.”
“Many people are experiencing cognitive impairments, and the brain is like a big black box. We have no clear understanding of what is happening there. We don’t know what molecular and cellular events represent the sequela of HIV in the brain. When someone receives antiretroviral therapy, is the virus suppressed in all cell types in the brain, or is there still ongoing replication? And, when therapy is interrupted what happens to the virus in the brain? Is there a persistent virus that can restart infection? These are all questions we want to answer.”