The Herpes Simplex Virus Type 1 Latency-Associated Transcript Affects Number and Distribution of Virus-Specific CD8+ T cells within the Latently Infected Vaginal Mucosa

Evidence from both animal models and humans suggest that successful control of HSV-1 and HSV-2 reactivation from latency, and the control of recurrent genital herpes, is associated with the presence of sustained local CD8⁺ T cells within the vaginal mucosal (VM) tissue. However, the mechanisms and the role of the viral genes that affect the number and function of VM-resident CD8⁺ T cells are unknown. The HSV Latency-Associated Transcript (LAT), the only viral gene that is abundantly transcribed during latency, increases reactivation. Our previous studies confirm that during latency of HSV-1 (McKrae strain) a higher number of CD8 T-cells are present in the trigeminal ganglia (TG) of LAT⁽⁺⁾ compared to LAT^(-) HSV-1 infected mice. HSV-specific CD8⁺ T cells were detected in the TGs of LAT⁽⁺⁾ HSV-1 infected mice. In this study, we extend these findings to determine how HSV-1 LAT⁽⁺⁾ virus affects the number and distribution of HSV-specific CD8⁺ T cells within the VM of latently infected mice. CD11c/eYFP transgenic mice were infected intravaginally with either LAT⁽⁺⁾ or LAT^(-) virus, the VM were harvested during latency and the number and distribution of CD8⁺ T cells were determined using immunohistochemistry (IHC) technique. Our results suggest an increase in the number of CD8⁺ T cells within the HSV-1 LAT⁽⁺⁾ infected VM compared to LAT^(-) VM. Furthermore, the distribution of CD8⁺ T cells within the HSV-1 LAT⁽⁺⁾ infected VM showed increased localization within the stroma and epithelial surface when compared to HSV-1 LAT^(-) infected VM. Together, these findings suggest that the HSV-1 LAT viral gene affects CD8⁺ T cells number and distribution within the VM of latently infected mice. These findings may constitute the first evidence of a mechanism whereby the HSV-1 LAT directly or indirectly affects HSV-specific CD8⁺ T cell number and distribution in the VM of a latently infected host.