MHV68 latency modulates host immune responses to H1N1 influenza virus (49.9)

Abstract

Abstract Human gammaherpesviruses such as Epstein-Barr virus (EBV) are clinically important pathogens, as diseases caused by gammaherpesvirus infection are a significant human health concern. Additionally, latent gammaherpesvirus infection is widespread, and can have a profound effect on subsequent immune responses. Murine gammaherpesvirus 68 (MHV68) is a natural rodent pathogen that has been used as a model to study the pathogenesis of human gammaherpesviruses. Like other herpesviruses, MHV68 causes acute infection and establishes life-long latency in the host. Recently, it has been shown that mice latently infected with MHV68 have resistance to unrelated pathogens in secondary infection models. We therefore hypothesized that latent MHV68 infection can modulate host response to H1N1 influenza virus, a serotype with high associated mortality rates in humans. To test this hypothesis, mice were infected intranasally with influenza virus following the establishment of MHV68 latency. Mice latently infected with MHV68 showed significantly higher survival of H1N1 influenza virus infection than mock-infected mice. Latent MHV68 infection led to lower influenza viral loads in the lungs, as well as decreased inflammatory pathology in the lungs. Collectively, our findings indicate that latent MHV68 infection has a protective effect against H1N1 influenza virus infection.