Scientists at UNC’s schools of public health and medicine will lead a five-year, $21.4 million research study that could result in more effective treatments for life-threatening virus infections of the lung and central nervous system. The program uses respiratory pathogens like the SARS coronavirus and pandemic influenza viruses and the neurotropic West Nile virus, which is causing considerable disease in the United States, to probe immune regulatory networks which regulate protective or pathogenic responses after infection.
The long-term goal of the project led by Ralph S. Baric and Mark T. Heise is to identify key immune regulatory genes and networks that control disease severity, communicate between immune compartments, and determine disease outcomes following infection. The program uses platforms that mimic human populations, focusing on how natural genetic variation regulates protective or pathogenic immune responses after infection.
Baric, a professor of epidemiology in the UNC Gillings School of Global Public Health and professor of microbiology and immunology in the UNC School of Medicine, and Heise, associate professor of genetics and microbiology and immunology in the medical school, are co-principal investigators of the study, “System immunogenetics of biodefense pathogens in the Collaborative Cross,” which is funded by the National Institute of Allergy and Infectious Diseases, part of the National Institutes of Health.
“These studies will transform our understanding of the virus-host interaction networks that regulate disease severity and protective immunity, leading to new therapeutic intervention strategies.”
“These studies will transform our understanding of the virus-host interaction networks that regulate disease severity and protective immunity, leading to new therapeutic intervention strategies,” Baric said. “Ultimately, the study design tests the promise of genetic medicine to predict and then alter disease outcomes following life-threatening virus infection in the lungs and central nervous system.”
Heise said the grant will provide new insights into why some people are susceptible to infection and others are highly resistant.
“This work should increase our understanding of how genetic variation within a population affects the host response to viral infection,” Heise said. “This understanding may lead to improved vaccination strategies or identify new targets for therapeutically modulating host immune responses.”
Significant variations in immune responses exist from person to person. And it is not clear how this variation regulates immune function in natural populations. The study will take advantage of new, genetically diverse mouse models (called the Collaborative Cross, developed at UNC) to identify novel genes and networks that regulate immunity and outcomes that follow infection.
Baric said understanding critical components of those immune responses to infection, as well as which host genes and pathways contribute to those responses, is crucial to the development of new treatments strategies.
By taking a population-based approach, he said, researchers can discover how and why aberrant immune responses happen in a fraction of a genetically diverse population. Ultimate outcomes from this research study could include personalized genetic medicine and broader-based intervention strategies.
Baric and Heise, long-time collaborators, will work with a team of viral immunologists, molecular biologists, geneticists and biostatisticians that include UNC professor Fernando Pardo Manuel de Villena; assistant professor Jason Whitmire; and postdoctoral fellow Martin Ferris, and research associate, Dr. Alan Whitmore, all in the Department of Genetics; and Amy Sims, research assistant professor of epidemiology.
UNC also will collaborate with researchers from the University of Washington, the Fred Hutchinson Cancer Center in Seattle and the Oregon Health Sciences Center.