학술논문
Estradiol Regulates Susceptibility following Primary Exposure to Genital Herpes Simplex Virus Type 2, while Progesterone Induces Inflammation.
Document Type
Article
Source
Subject
*HERPES simplex virus
*HERPESVIRUS diseases
*IMMUNE response
*ESTRADIOL
*PROGESTERONE
*CHEMOKINES
*COMMUNICABLE diseases
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Language
ISSN
0022-538X
Abstract
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 (E2), progesterone (P4), or a combination of both estradiol and progesterone (E+P) and infected intravaginally with HSV-2. With an inoculation dose of 105 PFU, the saline- and 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. E2-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 10³ and 10² 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 P4- and saline-treated animals within 24 h of inoculation. E2-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 P4-treated group. An analysis of the genes in the vaginal tissue showed that inflammation in the P4-treated group correlated with local induction of chemokines and chemokine receptors that were absent in the E2-treated mice and in uninfected P4-treated mice. The results show that sex hormones regulate initiation of infection and immune responses to genital HSV-2 infection. [ABSTRACT FROM AUTHOR]