A MOUSE MODEL FOR STUDIES OF MUCOSAL IMMUNITY TO VAGINAL INFECTION BYHERPES-SIMPLEX VIRUS TYPE-2

BACKGROUND: The role of mucosal immunity in defense of the female geni tal tract against pathogens such as herpes simplex virus-2 (HSV-2) is poorly understood. Here we explored the use of a new mouse model to de termine whether local immune events in the vagina of immune animals ma y protect them against genital herpes. EXPERIMENTAL DESIGN: The effect of the estrous cycle, pregnancy, and sex hormones on vaginal infectio n of adult mice by HSV-2 was determined by immunolabeling of virus pro teins. The immune response to infection was studied by immunolabeling of T lymphocytes, B lymphocytes, and plasma cells in the vagina of inf ected mice. RESULTS: Inoculation of attenuated virus (TK-HSV-2) or wil d-type virus (TK+HSV-2) into the vagina on day 6 of pregnancy or after treatment with Depo-Provera (DP) caused infection of the vaginal epit helium. In contrast, these viruses did not cause infection after vagin al inoculation at estrus, metestrus, or after treatment with Depo-Estr adiol. Infected mice showed immunolabeling of virus in the vaginal epi thelium from 24 hrs to 5 days after virus inoculation. The immune resp onse to infection included upregulation of class II MHC antigen in vag inal epithelium, CD8+ T cells in epithelium and stroma, and plasma cel ls and lymphoid nodules in the stroma. Mice that were infected with TK -HSV-2 did not exhibit infection of vaginal epithelium when challenged 6 weeks later with TK+HSV-2. CONCLUSIONS: Progesterone-dominated adul t mice become infected after intravaginal inoculation with HSV-2, but estradiol-dominated mice are refractory. Vaginal infection with attenu ated HSV-2 produces immunity that protects mice against later infectio n by wild-type virus. This immunity either prevents infection of vagin al epithelium or severely inhibits viral replication in the epithelium . The observations suggest that the E/DP-treated adult mouse should be a useful model for studies of mucosal immunity to vaginal infection b y HSV-2.