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Background: Genital herpes is one of the most common sexually transmitted infections in the United States. As genital herpes is incurable and contagious, individuals with genital herpes face the decision to disclose their status to potential sexual partners with each new relationship formed. Such disclosure places individuals with genital herpes in a position to face rejection, which is commonly reported as one of the most concerning aspects of having genital herpes. The present study seeks to further understand the nature of genital herpes disclosure by addressing two core aims: 1) to understand determinants of and reasons for disclosure and non-disclosure and 2) to explore the relationship between past partner reactions to a disclosure and future intentions to disclose. Methods: Data on genital herpes disclosure experiences were collected via an online questionnaire, which was distributed through a variety of online channels including social media websites and email lists. Individuals who self-identified as having genital herpes and were 18 years and older were eligible for participation. Results: In examining Aim 1, the majority of participants (80.4%) disclosed to their last sexual partner. Age, relationship length, type of relationship, and expectations of a partner's response were significantly associated with the decision to disclose at the bivariate level. Expectations of a partner's reaction (AOR = .20, 95% CI .074-.539) and relationship type (AOR = 8.31, 95% CI 1.96-35.32) remained significant in multivariable modeling, explaining 45.2% of the variance in disclosure. Respondents who reported being in socially committed relationships and those who expected more positive partner reactions to a disclosure were more likely to disclose. Disclosure was also significantly associated with many romantic relationship building activities (e.g., establishing an exclusive relationship) but largely not associated with the sexual progression of a relationship. The decision to disclose was commonly multi-faceted, with the majority of participants reporting more than one reason that they did or did not disclose. Primary reasons for disclosure included "I wanted to be honest", "To protect my partner from getting herpes", and "It's my partner's right to know", while the most common reasons for non-disclosure were "I was concerned my partner would react badly", "I was ashamed", and "I was concerned that my partner would have rejected me". Regarding Aim 2, participants reported low levels of negative reactions and perceived rejection in response to their last disclosure experience. Intentions to disclose in the future were high among those who anticipated future sex partners. Discussion: The decision to disclose is often multi-faceted, and relationship characteristics play a key role in the decision to disclose. Among those who did disclose in this study, the majority did not report negative repercussions, including bad partner reactions and rejection. Future studies should examine if individuals are able to accurately assess potential partner reactions in order to better understand the differences between those who choose not to disclose and those who choose to disclose but experience a negative partner reaction or rejection.

abstract: An estimated 267 million women worldwide are HSV-2 seropositive, including roughly 20% of reproductive-aged American women. HSV-2 is a neurotropic virus that establishes a persistent, life-long infection that increases risk for STI acquisition in individuals. The vaginal epithelium represents a critical first line of defense against infection, and during acute infection, underlying immune mechanisms in the epithelium may be critical to protect against disease pathogenesis. The recently identified pro-inflammatory cytokine IL-36gamma has been shown to be expressed at mucosal epithelia, including the female reproductive tract (FRT) and may be an important factor in host defense. Although IL-36gamma has been shown to be induced in the FRT after exposure to microbial products, the contributions of IL-36gamma to host defense mechanisms in response to this clinically relevant STI pathogen are not well understood. This dissertation describes the regulation of IL-36gamma in the FRT and explores its contribution to the host response against genital HSV-2 infection. To test the hypothesis that IL-36gamma is a key regulator of mucosal inflammation and immunity in the FRT, hormonal regulation of IL-36gamma in the FRT was investigated using estrogen- and progesterone-conditioned mice. From this preliminary study, it was shown that progesterone dampens IL36G expression relative to estrogen and may potentially increase susceptibility to infection. Next, the impact of IL-36gamma treatment on HSV-2 infection and replication in human 3-D vaginal epithelial cells was explored. In parallel, the impact of intravaginal IL-36gamma delivery on HSV-2 disease pathogenesis was evaluated using a lethal murine challenge model. IL-36gamma pre-treatment significantly limited HSV-2 replication in vitro and in vivo and was associated with transient neutrophil infiltration that corresponded with decreased disease severity and increased survival in mice. Last, the requirement for IL-36gamma in host defense was investigated utilizing IL-36gamma-/- mice in a lethal HSV-2 murine challenge model. Following infection, IL-36gamma-/- mice exhibited significantly impaired neutrophil recruitment, decreased overall survival time, and significantly increased viral neuroinvasion relative to wild type mice. Collectively, these data indicate that IL-36gamma is a crucial regulator of HSV-2-induced neutrophil infiltration and appears to function in a previously uncharacterized manner to limit viral neuroinvasion in genital HSV-2 disease pathogenesis. / Dissertation/Thesis / Doctoral Dissertation Molecular and Cellular Biology 2019

The recent discovery that T cells recognize different sets of herpes simplex virus type 1 and type 2 epitopes from seropositive symptomatic and asymptomatic individuals might lead to a fundamental immunologic advance in vaccine development against herpes infection and diseases. The newly introduced needle-free mucosal (i.e., topical ocular and intravaginal) lipopeptide vaccines provide a novel strategy that might target ocular and genital herpes and possibly provide 'heterologous protection' from HIV-1. Indeed, mucosal self-adjuvanting lipopeptide vaccines are easy to manufacture, simple to characterize, extremely pure, cost-effective, highly immunogenic and safe. In this review, we bring together recent published and unpublished data that illuminates the status of epitope-based herpes vaccine development and present an overview of our recent approach to an 'asymptomatic epitope'-based lipopeptide vaccine.

Background: The Division of Global HIV/AIDS at the Centers for Disease Control and Prevention (CDC) is working on a public health evaluation (PHE) in the eastern districts of Botswana. This PHE aims to evaluate the effectiveness of Project AIM, a group-level intervention designed to reduce HIV risk behaviors in youth ages 11 to 14, when combined with the regular Botswana Skills for Life Curriculum, a standard HIV prevention education curriculum in Botswana schools. In order to evaluate Project AIM, a self-report survey and a biological testing for herpes simplex virus type 2 (HSV-2) will be conducted. Methodology: Based on studies done on the psychosocial impact of HSV-2 diagnosis on asymptomatic individuals in the USA, the literature recommends providing pre and post counseling and education to individuals testing for genital herpes to help cope and diminish the psychosocial impact of the diagnosis. In order to prepare Botswana’s clinics and schools participating in the PHE to provide the support for newly diagnosed adolescents with HSV-2, guidance materials were developed for health care practitioners and school guidance teachers. Materials were created using Information Mapping technique to analyze, organize, and present the information, and the Microsoft Office Flesch Kinkade Grade Level (FK) tool to assess the readability levels of the materials. Results: Guidance materials were prepared using the 7±2 theoretical limit of human short-term memory information mapping rule, and the FK grade levels of 6.0 to 8.0 recommended readability scores. Guidance materials included information regarding HSV-2 symptoms, treatment, and prevention. They also included information on the PHE study, youth friendly health services, counseling and education, clinic referrals and contact information. Conclusions: The development of guidance materials for schools and clinic participants of the CDC PHE in Botswana will provide health practitioners and school guidance teachers with accurate HSV-2 information to counsel and educate student participants in this research study. The guidance materials should help students cope with potential psychosocial disorders associated with pre and post diagnosis of HSV-2.