Increased reactivation of murine gammaherpesvirus-68 during Heligmosomoides polygyrus infection

Abstract

Abstract A vast majority of people are infected with a herpesvirus. These viruses are double stranded DNA viruses that avoid eradication by the immune system by becoming latent. Certain signals, such as immune repression, can lead to reactivation of the virus. Reactivation of gamma herpesviruses is associated with pathologies, such as lymphomas and tumors. Past studies have shown that infection with helminths, extracellular parasitic worms, during gamma herpesvirus latency can cause reactivation. Helminths are known to secrete immunomodulatory factors that suppress host inflammation. The aim of the current study is to determine how prior helminth infection leads to increased reactivation of murine gammaherpesvirus-68 (MHV68). In this study, mice were or were not infected with Heligmosomoides polygyrus (HP), and then infected with MHV68. We found that infection with HP increased the reactivation of virus and the number of infected cells. However, there was no difference in acute replication of the virus between HP infected mice and HP uninfected mice. This suggests that the helminth infection specifically alters viral reactivation. The increased reactivation was only seen in a conventional mouse facility, but not in a barrier mouse facility, suggesting dependence on a microbiota component. Further work is required to determine how HP infection alters immune signals, such as IL-4 and STAT6 signaling, to cause increased MHV68 reactivation. Whether HP alters the permissiveness of cells to MHV68 infection should also be explored.