Grant: Doctoral Research Award - Priority Announcement - HIV/AIDS and/or STBBI

Herpes simplex virus-2 (HSV-2) is endemic in many countries and is estimated to infect 491 million people worldwide, approximately 13% of the total population. Infected individuals experience uncomfortable, reoccurring symptoms, and are at a higher risk of being co-infected with other genital infections such as HIV. Treatments for HSV-2 are currently limited, and there is no vaccine or cure. Thus, new areas of research to combat HSV-2 is needed. Our lab has previously found that endogenous retroviruses (ERVs) can protect mice from vaginal HSV-2 disease. ERVs are ancient retroviral sequences that originated from infection of non-human primates, and currently make up 8% and 10% of the human and mouse genomes, respectively. Although the exact mechanism of protection against HSV-2 is unanswered, preliminary data suggest that it is dependent on binding of the ERV envelope protein, and reducing the pathogenic effects of neutrophils in the vaginal tissue. I hypothesize that ERVs bind to proteins in the vaginal epithelium and this interaction, through host modulation, induces antiviral immunity against HSV-2. To test this hypothesis, I performed a co-immunoprecipitation (co-IP) assay to pull down mouse vaginal proteins that interact with ERVs. Using mass spectrometry (MS), I identified several receptors, including transferrin receptor-1 (TfR1), glucose transporter-1 (GLUT1), and mouse cationic amino acid transporter-1 (mCAT1). I am currently investigating how these interactions contribute to the protection phenotype. I am also investigating the role of ERVs in regulating pathogenic neutrophils in the vaginal tissue in the same model. Furthermore, I am working with our collaborator in OBGYN to identify human ERVs that are associated with the control of HSV-2 reactivation in humans. This work will contribute to the development of new therapeutics for HSV-2 and broaden our knowledge of how ERVs modulate the host, which can be applied to other areas of health research.