Estradiol regulates susceptibility following primary exposure to genital herpes simplex virus type 2, while progesterone induces inflammation.
We report here that sex hormones modulate susceptibility to a sexually transmitted viral agent, herpes simplex virus type 2 (HSV-2), in a mouse model. Ovariectomized mice were administered either saline (control), estradiol (E(2)), progesterone (P(4)), or a combination of both estradiol and progesterone (E+P) and infected intravaginally with HSV-2. With an inoculation dose of 10(5) PFU, the saline- and P(4)-treated mice were found to be highly susceptible to genital HSV-2 infection. Both groups had extensive pathology and high viral titers in vaginal secretions, and 100% of mice succumbed by day 4 postinfection. E(2)-treated mice were protected from HSV-2 infection at the same dose and did not display any vaginal pathology or viral shedding. There was a slow progression of genital pathology in the combination hormone-treated group, along with prolonged viral shedding; 80% of animals succumbed by day 13. With lower inoculation doses of 10(3) and 10(2) PFU, 50 and 100%, respectively, of the combination hormone-treated mice survived. Localization of HSV-2 infection showed extensive infection in the vaginal epithelium of P(4)- and saline-treated animals within 24 h of inoculation. E(2)-treated animals were clear of infection, while the E+P-treated group had focal infection at 24 h that had progressed extensively by day 3. Infection was accompanied by persistent inflammation and infiltration of neutrophils in the P(4)-treated group. An analysis of the genes in the vaginal tissue showed that inflammation in the P(4)-treated group correlated with local induction of chemokines and chemokine receptors that were absent in the E(2)-treated mice and in uninfected P(4)-treated mice. The results show that sex hormones regulate initiation of infection and immune responses to genital HSV-2 infection.
Gillgrass
Amy E
AE
Department of Pathology, Center for Gene Therapeutics, MDCL 4014, McMaster University, 1200 Main St. West, Hamilton, Ontario, Canada.
Fernandez
Sherie A
SA
Rosenthal
Kenneth L
KL
Kaushic
Charu
C
D000818:Animals; D004195:Disease Models, Animal; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006558:Herpes Genitalis / Q000209:etiology* / Q000473:pathology / Q000821:virology; D018258:Herpesvirus 2, Human / Q000187:drug effects* / Q000302:isolation & purification / Q000472:pathogenicity*; D007249:Inflammation / Q000209:etiology; D051379:Mice; D008810:Mice, Inbred C57BL; D010052:Ovariectomy; D011374:Progesterone / Q000494:pharmacology*; D014621:Vagina / Q000473:pathology / Q000821:virology; D014774:Virulence / Q000187:drug effects
D011374:Progesterone; D004958:Estradiol