Gammaherpesviruses such as Epstein-Barr virus (EBV), Kaposi's sarcomaassociated virus (KSHV), and murine gammaherpesvirus 68 (MHV68) establish latent infection in B cells, macrophages, and nonlymphoid cells and can induce both lymphoid and nonlymphoid cancers. Research on these viruses has relied heavily on immortalized B cell and endothelial cell lines. Therefore, we know very little about the cell type-specific regulation of virus infection. We have previously shown that treatment of MHV68-infected macrophages with the cytokine interleukin-4 (IL-4) or challenge of MHV68-infected mice with an IL-4-inducing parasite leads to virus reactivation. However, we do not know if all latent reservoirs of the virus, including B cells, reactivate the virus in response to IL-4. Here, we used an in vivo approach to address the question of whether all latently infected cell types reactivate MHV68 in response to a particular stimulus. We found that IL-4 receptor expression on macrophages was required for IL-4 to induce virus reactivation but that it was dispensable on B cells. We further demonstrated that the transcription factor STAT6, which is downstream of the IL-4 receptor and binds the virus gene 50 N4/N5 promoter in macrophages, did not bind to the virus gene 50 N4/N5 promoter in B cells. These data suggest that stimuli that promote herpesvirus reactivation may affect latent virus only in particular cell types but not in others.
ASJC Scopus subject areas
- Insect Science