This proposal describes a 5-year training program for the development of an independent researcher in the area of reproductive infectious diseases, specifically genital herpes infections in women. This award would provide the applicant valuable didactic training and human and animal research experience from a multidisciplinary mentoring team. An important contributor to the epidemic spread of herpes simplex virus type 2 (HSV-2) is its high frequency of asymptomatic shedding in the genital tract, as transmission of the virus usually occurs during these periods of subclinical reactivation. Therefore, an improved understanding of the risk factors associated with HSV-2 reactivation and shedding are urgently needed. In addition, it is important to improve our understanding of the pathomechanisms associated with HSV-2 reactivation. As hormonal contraceptives are used by more than 100 million women worldwide and bacterial vaginosis is a very common cause of vaginal symptoms, even modest associations with genital shedding of HSV-2 would result in substantial attributable risks for transmission of the virus. Therefore, this research will assess: 1. The effects of hormonal contraceptive use, either oral contraceptive pills or depo-medroxyprogesterone, on daily genital tract shedding of HSV-2 compared to women who do not use hormonal contraceptives in a natural history study of 102 women 2. The effects of asymptomatic bacterial vaginosis on the daily genital tract shedding of HSV-2 by evaluating shedding frequency before and after treatment of bacterial vaginosis in 30 women 3. The effects of exogenous sex steroids on the capacity of HSV-specific T lymphocytes to inhibit HSV reactivation in sensory neurons and subsequent shedding on epithelial surfaces in a murine model.

National Institute of Health (NIH)
National Institute of Allergy and Infectious Diseases (NIAID)
Mentored Patient-Oriented Research Career Development Award (K23)
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Study Section
Acquired Immunodeficiency Syndrome Research Review Committee (AIDS)
Program Officer
David, Hagit S
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Magee-Women's Research Institute and Foundation
United States
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Stoner, Kevin A; Reighard, Seth D; Vicetti Miguel, Rodolfo D et al. (2012) Recalcitrance of bacterial vaginosis among herpes-simplex-virus-type-2-seropositive women. J Obstet Gynaecol Res 38:77-83
Vicetti Miguel, Rodolfo D; Chivukula, Mamatha; Krishnamurti, Uma et al. (2011) Limitations of the criteria used to diagnose histologic endometritis in epidemiologic pelvic inflammatory disease research. Pathol Res Pract 207:680-5
Reighard, Seth D; Sweet, Richard L; Vicetti Miguel, Claudia et al. (2011) Endometrial leukocyte subpopulations associated with Chlamydia trachomatis, Neisseria gonorrhoeae, and Trichomonas vaginalis genital tract infection. Am J Obstet Gynecol 205:324.e1-7
Vicetti Miguel, Rodolfo D; Sheridan, Brian S; Harvey, Stephen A K et al. (2010) 17-beta estradiol promotion of herpes simplex virus type 1 reactivation is estrogen receptor dependent. J Virol 84:565-72
Frank, Gregory M; Lepisto, Andrew J; Freeman, Michael L et al. (2010) Early CD4(+) T cell help prevents partial CD8(+) T cell exhaustion and promotes maintenance of Herpes Simplex Virus 1 latency. J Immunol 184:277-86
Sheridan, Brian S; Cherpes, Thomas L; Urban, Julie et al. (2009) Reevaluating the CD8 T-cell response to herpes simplex virus type 1: involvement of CD8 T cells reactive to subdominant epitopes. J Virol 83:2237-45
Leyland, Bridget; Kennedy, Margaret R; Wimberly, Yolanda H et al. (2009) Serologic detection of herpes simplex virus type 2 antibodies among pregnant women using a point-of-care test from Focus Diagnostics. J Clin Virol 44:125-8
Cherpes, Thomas L; Hillier, Sharon L; Meyn, Leslie A et al. (2008) A delicate balance: risk factors for acquisition of bacterial vaginosis include sexual activity, absence of hydrogen peroxide-producing lactobacilli, black race, and positive herpes simplex virus type 2 serology. Sex Transm Dis 35:78-83
Cherpes, Thomas L; Busch, James L; Sheridan, Brian S et al. (2008) Medroxyprogesterone acetate inhibits CD8+ T cell viral-specific effector function and induces herpes simplex virus type 1 reactivation. J Immunol 181:969-75
Cherpes, T L; Marrazzo, J M; Cosentino, L A et al. (2008) Hormonal contraceptive use modulates the local inflammatory response to bacterial vaginosis. Sex Transm Infect 84:57-61

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