Intravaginal administration of herpes simplex virus type 2 to mice leads to infection of several neural and extraneural sites

Female mice have been used extensively to study mucosal immunity against herpes simplex virus type 2 (HSV-2) infection of the vagina, but comparatively little is known about the spread of this virus to other tissues. Here the authors have used immunolabeling to demonstrate that HSV-2 infected the vaginal epithelium; the epithelium covering the vulva, perineum, and anal canal; and perineal hair follicles and sebaceous glands. The kinetics and basal localization of the immunolabeling indicated that the virus spread horizontally within the epithelial layer, starting in the vagina and then proceeding to the distal epithelial sites. HSV-2 also spread from the vagina to multiple neuronal sites including the paracervical ganglia (PCG), which are the major autonomic ganglia of the pelvis. The authors demonstrated both sympathetic and parasympathetic neurons in the PCG by labeling of acetylcholinesterase and tryosine hydroxlyase, and noted that infection was limited mainly or entirely to parasympathetic neurons. Infection of the PCG was correlated with the presence of virus in the autonomic ganglia in the walls of the rectum and urinary bladder, which in turn correlated with distention of these organs and retention of urine and feces. HSV-2 infection was also detected in cell bodies and axons in the lumbosacral sympathetic chain, in lumbosacral dorsal root ganglia, and in the dorsal portions of the lumbar spinal cord. Collectively, the data show that vaginal HSV-2 infection in mice leads to subsequent infection of multiple neural and epithelial sites. This information should be useful for development of a mouse model that can be used to study HSV-2 latency and for development of therapeutic vaccines to prevent recurrent infections.