Characterizing the effect of type I interferon signaling within regulatory T cells in HSV-2 infection

Abstract Herpes simplex virus type-2 (HSV-2) is a lifelong, recurrent sexually transmitted infection that affects about 13% of the world population between ages 13–49. There is currently no available vaccine for HSV-2 and understanding the nuances of cell-mediated immunity is crucial to developing improved therapeutics and vaccines. HSV-2 infection induces a potent, localized type I interferon (TIIFN) signaling cascade that can stimulate both innate and adaptive antiviral effector responses. Interestingly, regulatory T cells (Tregs), an immunosuppressive CD4+ T cell subset, also respond to TIIFNs. TIIFNs have previously been shown to transiently inhibit Tregs early during a systemic lymphocytic choriomeningitis virus (LCMV) infection to promote the development of antiviral CD4+ and CD8+ T cell responses, and Tregs that lack the interferon alpha receptor (IFNAR) have enhanced suppressive function. The role of TIIFNs in a mucosal infection such as HSV-2 is unclear and studying the tissue-specific effects of TIIFNs warrants further study. To investigate the role of TIIFN signaling within Tregs in the context of HSV-2, we infected IFNARfl/fl x FoxP3Cre mice intravaginally with attenuated or WT HSV-2 and assessed phenotypic Treg markers and viral titers within the vaginal tract by flow cytometry and plaque assays, respectively. Preliminary data indicates that WT, and not attenuated HSV-2 infected mice show enhanced disease progression and increased viral titers. This suggests that TIIFN signaling in Tregs could be aiding in mediating protection early in HSV-2 infection. NIH R01AI141435