By Guest Author • March 27, 2024
Written by April Houston, MSW, MPH, knowledge translation & communications director, HLB-SIMPLe Research Alliance, Division of Infectious Diseases, WashU School of Medicine
Scientists from Washington University have uncovered new insights into how HIV weakens the immune system of those it infects. Their findings were published in a recent edition of the journal Cell.
CD4 T lymphocytes, also known as T cells, are white blood cells found in mammals that fight off disease-causing microorganisms. They are crucial to the functioning of our immune systems. When HIV invades a human body, it depletes T cells in the blood, progressively damaging the immune system. If the amount of T cells gets below a certain threshold, the infected individual will be diagnosed with AIDS.
Until now, scientists did not understand how exactly HIV depleted T cells.
“The simplest explanation is that the virus infects the cells directly to deplete them, but this is not correct,” explained Associate Professor of Medicine and of Pathology and Immunology, Liang Shan, a WashU Public Health Faculty Scholar and corresponding author of the groundbreaking study.
With their research, Shan and team have unearthed the culprit: an overactive immune response triggered by the virus.
When HIV enters the body, it activates the CARD8 inflammasome, an immune receptor in the body which responds to infections by alerting the immune system to the invading pathogen. This activation leads to a chain reaction resulting in the death of immune cells, not directly from the virus itself, but from the body’s own defensive response gone awry.
To understand this, the researchers performed experiments in mice engineered to have human-like immune systems but deficient in CARD8. These mice did not experience the usual depletion of T cells, despite having high levels of the virus.
Before HIV began infecting humans, there was SIV (simian immunodeficiency virus) in certain primates. Scientists believe that HIV may have jumped from these primates to humans.
“Some primate species can have SIV, but they don’t develop AIDS,” Shan explained. “They are known as ‘non-pathogenic hosts’, and they carry mutations that make CARD8 ineffective. Their T-cells are never lost.”
“This is a really important discovery and a huge scientific achievement,” said Professor of Medicine in WashU’s Division of Infectious Diseases, Elvin Geng, also co-director of the Center for Dissemination and Implementation.
By understanding and potentially manipulating the function of CARD8, scientists may be able to prevent the immune system from damaging its own cells during HIV infection, which could stop the virus in its tracks. This research from Liang and team reveals a promising new direction in the quest to defeat HIV.