This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Gillgrass, A. E.
Right arrow Articles by Kaushic, C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Gillgrass, A. E.
Right arrow Articles by Kaushic, C.

 Previous Article  |  Next Article 

Journal of Virology, March 2005, p. 3107-3116, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.3107-3116.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Estradiol Regulates Susceptibility following Primary Exposure to Genital Herpes Simplex Virus Type 2, while Progesterone Induces Inflammation

Amy E. Gillgrass, Sherie A. Fernandez, Kenneth L. Rosenthal, and Charu Kaushic*

Center for Gene Therapeutics, Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ontario, Canada

Received 21 October 2004/ Accepted 14 December 2004

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 P4-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.

* Corresponding author. Mailing address: Department of Pathology, Center for Gene Therapeutics, MDCL 4014, McMaster University, 1200 Main St. West, Hamilton, Ontario, Canada L8N 3Z5. Phone: (905) 525-9140, ext. 22988. Fax: (905) 522-6750. E-mail: kaushic{at}mcmaster.ca.

Journal of Virology, March 2005, p. 3107-3116, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.3107-3116.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



This article has been cited by other articles:

  • MacDonald, E. M, Savoy, A., Gillgrass, A., Fernandez, S., Smieja, M., Rosenthal, K. L, Ashkar, A. A, Kaushic, C. (2007). Susceptibility of Human Female Primary Genital Epithelial Cells to Herpes Simplex Virus, Type-2 and the Effect of TLR3 Ligand and Sex Hormones on Infection. Biol. Reprod. 77: 1049-1059 [Abstract] [Full Text]  
  • Iijima, N., Linehan, M. M., Saeland, S., Iwasaki, A. (2007). Vaginal epithelial dendritic cells renew from bone marrow precursors. Proc. Natl. Acad. Sci. USA 104: 19061-19066 [Abstract] [Full Text]  
  • Seavey, M. M., Mosmann, T. R. (2006). Paternal Antigen-Bearing Cells Transferred during Insemination Do Not Stimulate Anti-Paternal CD8+ T Cells: Role of Estradiol in Locally Inhibiting CD8+ T Cell Responses. J. Immunol. 177: 7567-7578 [Abstract] [Full Text]  
  • Yim, K. C., Carroll, C. J., Tuyama, A., Cheshenko, N., Carlucci, M. J., Porter, D. D., Prince, G. A., Herold, B. C. (2005). The Cotton Rat Provides a Novel Model To Study Genital Herpes Infection and To Evaluate Preventive Strategies. J. Virol. 79: 14632-14639 [Abstract] [Full Text]  
  • Gillgrass, A. E., Tang, V. A., Towarnicki, K. M., Rosenthal, K. L., Kaushic, C. (2005). Protection against Genital Herpes Infection in Mice Immunized under Different Hormonal Conditions Correlates with Induction of Vagina-Associated Lymphoid Tissue. J. Virol. 79: 3117-3126 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»