title: Loss of the type I interferon pathway increases vulnerability of mice to genital herpes simplex virus 2 infection.
abstract: The mouse model of genital herpes relies on medoxyprogesterone treatment of female mice to render the vaginal lumen susceptible to inoculation with herpes simplex virus 2 (HSV-2). In the present study, we report that mice deficient in the A1 chain of the type I interferon receptor (CD118(-/-)) are susceptible to HSV-2 in the absence of medroxyprogesterone preconditioning. In the absence of hormone pretreatment, 2,000 PFU of a clinical isolate of HSV-2 was sufficient to establish a productive infection in the vagina of 75% ± 17% and in the spinal cord of 71% ± 14% of CD118(-/-) mice, whereas the same dose of HSV-2 replicated to detectable levels in only 13% ± 13% of vaginal samples and 0% of spinal cord samples from wild-type mice, as determined at day 5 postinfection. The susceptibility to HSV-2 infection in the CD118(-/-) mice was associated with a significant reduction in the infiltration of HSV-specific cytotoxic T lymphocytes into the vaginal tissue, the local production of gamma interferon (IFN-γ), and the expression of T cell-recruiting chemokines CCL5, CXCL9, and CXCL10. Collectively, the results underscore the significant contribution of type I IFNs in resistance to genital HSV-2 infection.
authors.affiliation: Department of Microbiology and Immunology, The University of Oklahoma Health Sciences Center, Oklahoma City, Oklahoma 73104, USA.
authors.forename: Christopher D
authors.initials: CD
authors.lastname: Conrady
authors.forename: William P
authors.initials: WP
authors.lastname: Halford
authors.forename: Daniel J J
authors.initials: DJ
authors.lastname: Carr
mesh_terms: D000282:Administration, Intravaginal; D000818:Animals; D005260:Female; D006558:Herpes Genitalis / Q000276:immunology* / Q000503:physiopathology / Q000821:virology; D006561:Herpes Simplex / Q000821:virology; D018258:Herpesvirus 2, Human / Q000378:metabolism / Q000472:pathogenicity*; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit / Q000172:deficiency* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D013116:Spinal Cord / Q000276:immunology / Q000821:virology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D014621:Vagina / Q000276:immunology / Q000821:virology; D014779:Virus Replication
chemical_list: D007370:Interferon Type I; D053680:Leukemia Inhibitory Factor Receptor alpha Subunit