U.Va. Researchers Receive $8.2 Million Grant to Study Interaction of Viruses with the Immune System

September 3, 2009 — Amid fears of a swine flu pandemic possibly killing millions of people worldwide, investigators at The Beirne B. Carter Center for Immunology Research at the University of Virginia Health System are studying how the human immune system works to clear viruses from the body.

"With the swine flu, as with the avian flu, the body responds to a viral infection by sending cells to the site of the infection to kill the invading cells. However, these viruses may have the ability to manipulate a person's own immune system, which in turn causes the body to inflict more harm on itself," said Dr. Thomas Braciale, director of the Carter Center fand a professor of pathology and microbiology at the U.Va. School of Medicine.

An $8.2 million grant from the National Institute of Allergy and Infectious Disease will allow Braciale will lead an investigative team from U.Va. and Dartmouth University Medical Center looking at how the response of the immune system to clear virus infection can also injure the body.

Interleukin-10 (IL10) is the anti-inflammatory cytokine responsible for stopping the body's immune response from causing injury to itself. If the IL10 stops the body's immune response too soon, the immune system won't produce enough T-cells to fight the infection. If the IL10 stops the body's response too late, a person could be more susceptible to additional bacterial infections in addition to damage from the inflammation response.

In novel H1N1 infection, the virus may cause the body to stop producing IL10 at the site of the viral infection, which in turn signals the immune system to send more infection-fighting T-cells to the site of infection. Uncontrolled, the T-cells can cause additional inflammation and damage to the body – often far greater damage than the virus itself would cause.

"That may be why in many cases we see young, healthy people are the ones who are dying from H1N1. Because their bodies are producing such a strong response to the virus, it is doing major harm to these people," Braciale said.

IL10 is produced in large volume in a person's liver to control the amount of inflammation in the liver. In models for Hepatitis C, the virus can suppress T-cells but trick the liver to make excess IL10.

"Here's a molecule in two different sites in the body that can have two different effects," Braciale said. "We are also going to look at how the immune system causes liver damage during hepatitis C infection and how the immune system controls chronic infections with viruses."

He is hopeful the study will lead to the development of new treatments to better support the body's response to viral infections by managing the immune system to keep it from causing more harm than good.

"Timing is everything when it comes to inflammation response with IL10. We hope our work can lead to a better understanding of the immune system and how viruses manipulate it against our bodies," Braciale said.

U.Va. scientists involved in the project include Carter Immunology Center members Young S. Hahn, a professor of microbiology, Michael Brown, an associate professor of medicine; Sung-Sang Sung, an associate professor of medicine and U.Va. Cytometry Core director Joanne Lannigan.