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Journal of Virology, March 2005, p. 3117-3126, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.3117-3126.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Protection against Genital Herpes Infection in Mice Immunized under Different Hormonal Conditions Correlates with Induction of Vagina-Associated Lymphoid Tissue

Amy E. Gillgrass, Vera A. Tang, Kate M. Towarnicki, Kenneth L. Rosenthal, and Charu Kaushic*

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

Received 20 October 2004/ Accepted 13 December 2004

The present study was undertaken to examine the effect of the hormonal environment on immunization with an attenuated strain of herpes simplex virus type 2 (HSV-2 TK) and subsequent protection against challenge. Ovariectomized mice were administered saline (S; control), estradiol (E2), progesterone (P4), or a combination of estradiol and progesterone (E+P) and immunized intravaginally (IVAG) with HSV-2 TK. Three weeks later, the immunized mice were challenged IVAG with wild-type HSV-2. Mice that were immunized following E treatment were not protected, whereas complete protection against the challenge was seen in mice from the S- and P4-treated groups. In the P4-treated group, 15% of mice developed chronic pathology following TK immunization. Interestingly, about 40% of the E+P-treated mice were also protected. Upon examination of viral shedding in the vaginal secretions, it was clear that protection against challenge was dependent on the ability of the TK virus to cause productive genital infection under different hormonal conditions. In the protected mice (the S and P groups and part of the E+P group), induced vagina-associated lymphoid tissues composed of CD11c+ dendritic cells and CD3+ and CD4+ T cells were formed transiently in the vaginal lamina propria from day 2 to day 5 postchallenge. These aggregates were absent in the unprotected mice (the E group and part of the E+P group). Significant HSV-2-specific activation of lymphocytes was observed in the local draining lymph nodes of protected mice. This response was absent in the unprotected groups. High titers of gB-specific local immunoglobulin A (IgA) antibodies were present in the vaginal secretions of S- and P4-treated immunized mice following HSV-2 challenge. The S-treated group of mice also had high gB-specific IgG titers. These studies show that sex hormones modify the induction of protective immune responses following IVAG immunization.


* Corresponding author. Mailing address: Department of Pathology, 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. 3117-3126, Vol. 79, No. 5
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.5.3117-3126.2005
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]  
  • Gill, N., Deacon, P. M., Lichty, B., Mossman, K. L., Ashkar, A. A. (2006). Induction of Innate Immunity against Herpes Simplex Virus Type 2 Infection via Local Delivery of Toll-Like Receptor Ligands Correlates with Beta Interferon Production.. J. Virol. 80: 9943-9950 [Abstract] [Full Text]  
  • Gillgrass, A. E., Fernandez, S. A., Rosenthal, K. L., Kaushic, C. (2005). Estradiol Regulates Susceptibility following Primary Exposure to Genital Herpes Simplex Virus Type 2, while Progesterone Induces Inflammation. J. Virol. 79: 3107-3116 [Abstract] [Full Text]