title: Herpes simplex virus type 2-mediated disease is reduced in mice lacking RNase L.
abstract: RNase L helps mediate the antiviral state induced by type I interferons (IFNalphabeta). Although herpes simplex virus (HSV) encodes inhibitors of the IFNalphabeta-induced antiviral response, the IFNalphabeta 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.
authors.affiliation: Department of Molecular Microbiology and Immunology, Saint Louis University School of Medicine, 1402 S. Grand Blvd., St. Louis, MO 63104, USA. duers007@umn.edu
authors.forename: Rebecca J
authors.initials: RJ
authors.lastname: Duerst
authors.forename: Lynda A
authors.initials: LA
authors.lastname: Morrison
mesh_terms: D000818:Animals; D001835:Body Weight; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002490:Central Nervous System / Q000821:virology; D004195:Disease Models, Animal; D004722:Endoribonucleases / Q000235:genetics* / Q000502:physiology*; D005260:Female; D005836:Genitalia, Female / Q000473:pathology; D006561:Herpes Simplex / Q000201:enzymology / Q000276:immunology* / Q000473:pathology / Q000821:virology; D018258:Herpesvirus 2, Human / Q000276:immunology / Q000472:pathogenicity; D007113:Immunity, Innate; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D014774:Virulence
chemical_list: D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease