Herpes simplex virus type 2-mediated disease is reduced in mice lacking RNase L

RNase L helps mediate the antiviral state induced by type I interferons (IFNαβ). Although herpes simplex virus (HSV) encodes inhibitors of the IFNαβ-induced antiviral response, the IFNαβ system serves the body as a first line of defense against HSV. We investigated whether RNase L limits HSV-2 replication and virulence. RNaseL−/− and wild-type C57BL/6 mice were infected intravaginally with HSV-2 strain 333. Although initial replication in the genital epithelium was similar, mice lacking RNase L developed less severe genital and neurologic disease than wild-type mice, survived longer, and contained lower viral titers in the nervous system. CD4+ T cell infiltration into the genital tract and spinal cord of RNase L−/− mice was reduced, suggesting that a restricted inflammatory response may account for reduction in disease. Thus, RNase L does not play a significant role in control of HSV-2 infection in vivo; instead, RNase L may regulate aspects of the inflammatory response that contribute to disease.