CPB 697 RESEARCH SEMINAR
Erik S. Barton, PhD
Assistant Professor of Biological Sciences
“Herpesvirus Latency Protects the Host from Bacterial Infection:
Latency as Mutualistic Symbiosis”
Thursday, February 8, 2007
VPTH 112
3:30 p.m.
Abstract:
Herpesviruses establish lifelong latent infection and are the most prevalent chronic infections of humans. Although the antiviral immune response during latency was historically thought to be a state of quiescent memory, there is increasing evidence of chronic virus-specific lymphocyte activation during latency. However, the precise immunologic effects of viral latency are not defined, and potential beneficial consequences of viral latency have not been explored. We found that latent infection with either murine gammaherpesvirus 68 (gammaHV68) or murine cytomegalovirus (MCMV), close relatives of the human pathogens Epstein-Barr Virus (EBV) and cytomegalovirus (HCMV), triggers prolonged systemic activation of tissue-resident macrophages and resistance to infection with Listeria monocytogenes and Yersinia pestis. A gammaHV68 mutant which undergoes efficient acute infection but cannot establish latency did not induce bacterial resistance. Latency-induced protection lasted for greater than three months and required interferon gamma, but was independent of the class I antigen presentation pathway and was not mediated directly by CD4+ or CD8+ T lymphocytes. Thus, latent herpesvirus infection protects the host from subsequent infections by upregulating the setpoint of innate immunity. Given the coevolution between herpesviruses and their hosts and the high seroprevalence of herpesvirus infection in humans, our data suggest that latent infection can be viewed as an endosymbiotic relationship.