NIH awards WSU researcher $3M to study inflammatory response during virus infection

Washington State University researcher Santanu Bose has been awarded a $3.04 million grant from the National Institutes of Health for research that could lead to new treatment options for human respiratory syncytial virus, commonly known as RSV, and other respiratory viral infections.

RSV is a leading cause of respiratory illness worldwide, particularly among infants, young children and people with weakened immune systems. It can cause pneumonia and bronchiolitis, and infections early in life have been linked to an increased risk of developing chronic respiratory conditions such as asthma.

The five-year grant will support a project aimed at understanding how the body's own immune response to RSV can cause significant lung damage leading to inflammatory diseases like pneumonia and how that process may be blocked by therapeutic agents to combat lung disease. The project will be conducted in collaboration with Sid Balachandran, director of the Center for Immunology at Fox Chase Cancer Center, Philadelphia.

"Our immune response to RSV is a double-edged sword," said Bose, a professor of immunology and infectious diseases in WSU's College of Veterinary Medicine. "We're trying to understand why the immune response sometimes goes too far and ends up damaging the lungs by inflammation. In many ways, the body could eliminate the virus with a regulated inflammatory response, but instead it responds with excessive inflammation, , which ends up harming the host."

When RSV infects cells, the body's immune system responds with a process known as lytic cell death, also known as necroptosis and pyroptosis, in which infected cells rupture and release their contents into surrounding tissue. While the response can help fight infection, it can also lead to excessive inflammation that damages the lungs and contributes to diseases such as pneumonia.

Bose's laboratory has already identified a key immune-signaling pathway involved in triggering "damaging" lytic cell death during RSV infection. The new grant will help provide a better understanding of how this cellular immune pathway works and explore therapeutic ways to block the harmful cellular signals that drive the damaging inflammatory response leading to lung disease. This may result in development of effective host-directed therapeutics to combat viral pneumonia.

Although the grant is focused on RSV, Bose said the work could have broader implications for other viruses that are related to RSV.

"Often it's not the virus itself that causes the greatest damage," Bose said. "A lot of the harm comes from the body's response to infection. If we can learn how to control that response, it could help us develop new treatments not only for RSV but for other serious respiratory and non-respiratory viral infections as well."