Epstein-Barr virus IL-10 gene expression by a recombinant murine gammaherpesvirus in vivo enhances acute pathogenicity but does not affect latency or reactivation

Abstract

Background Many viral genes affect cytokine function within infected hosts, with interleukin 10 {(IL-10)} as a commonly targeted mediator. {Epstein-Barr} virus {(EBV)} encodes an {IL-10} homologue {(vIL-10)} expressed during productive (lytic) infection and induces expression of cellular {IL-10} {(cIL-10)} during latency. This study explored the role of {vIL-10} in a murine gammaherpesvirus {(MHV)} model of viral infection. Methods The {EBV} {vIL-10} gene was inserted into {MHV-76,} a strain which lacks the ability to induce {cIL-10,} by recombination in transfected mouse cells. Mice were infected intranasally with the recombinant, {vIL-10-containing} {MHV-76} or control virus strains and assayed at various days post infection for lung virus titer, spleen cell number, percentage of latently infected spleen cells and ability to reactivate virus from spleen cells. Results Recombinant murine gammaherpesvirus expressing {EBV} {vIL-10} rose to significantly higher titers in lungs and promoted an increase in spleen cell number in infected mice in comparison to {MHV} strains lacking the {vIL-10} gene. However, {vIL-10} expression did not alter the quantity of latent virus in the spleen or its ability to reactivate. Conclusions In this mouse model of gammaherpesvirus infection, {EBV} {vIL-10} appears to influence acute-phase pathogenicity. Given that {EBV} and {MHV} wild-type strains contain other genes that induce {cIL-10} expression in latency (e.g. {LMP-1} and M2, respectively), {vIL-10} may have evolved to serve the specific role in acute infection of enlarging the permissive host cell population, perhaps to facilitate initial survival and dissemination of viral-infected cells.