Indeed, the DRG recruited activated T cells in response to infection, which are required to limit viral replication and cell death (Anti-CD8 impairs clearance of herpes simplex virus from the nervous system: implications for the fate of virally infected neurons.Type I IFN suppresses Cxcr2 driven neutrophil recruitment into the sensory ganglia during viral infection.Type I IFN suppresses Cxcr2 driven neutrophil recruitment into the sensory ganglia during viral infection.Orally acquired HSV-1 can spread to multiple sensory and autonomic ganglia, thus demonstrating a broad neuronal tropism throughout the head, neck, and torso (Latency of herpes simplex virus type-1 in human geniculate and vestibular ganglia is associated with infiltration of CD8+ T cells.Distribution of herpes simplex virus type 1 and varicella zoster virus in ganglia of the human head and neck.Isolation of latent herpes simplex virus from the superior cervical and vagus ganglions of human beings.Herpes simplex virus type I reactivation as a cause of a unilateral temporary paralysis of the vagus nerve.Herpes esophagitis in healthy adults and adolescents: report of 3 cases and review of the literature.Chronic intestinal pseudo-obstruction related to viral infections.DNA viruses in the pathogenesis of sporadic chronic idiopathic intestinal pseudo-obstruction.C57BL/6 (B6) female mice were purchased from Charles River Laboratories or the National Cancer Institute and subsequently bred and housed at Yale University. (E) Gastrointestinal (GI) transit time was determined 7 d.p.i. Scale bars represent 50 μm. I. Statistical significance was measured by a Mann-Whitney test (exact) (A) or by a log-rank (Mantel-Cox) test (B), (D) Whole-mount microscopy images of the large intestine musculara showing enteric neurons (magenta), glial cells (teal), and nuclear DAPI staining (blue) at 9 d.p.i. ; Writing – Review & Editing, W.K.-H., B.Y., Y.K., T.L.H., and A.I. The spread of HSV-1 beyond the sensory nervous system and the resulting broader spectrum of disease are not well understood. No inflammation or infection of the brain was evident. Using a mouse model of genital herpes, we found that HSV-1-infection-associated lethality correlated with severe fecal and urinary retention. Using Ingenuity Pathway Analysis (IPA) to categorize the downregulated genes, we observed that canonical pathways pertaining to neuronal signaling such as “calcium signaling,” “axonal guidance signaling,” and “cardiac β-adrenergic signaling” were enriched, which is consistent with a defect in autonomic neuronal signaling and smooth muscle peristalsis ((A and B) Volcano plots displaying the fold change and p value of differentially expressed genes (≥2-fold change and adjusted p value < 0.05) in the large intestine musculara (A) and DRG (B) in HSV-1-infected mice compared to mock-infected controls. ; Resources, K.S.-B., A.R., and T.L.H. Mice are segregated into separate groups based on their GI motility status as shown in (A). Mice were monitored for at least 4.5 hr and the time required to pass the carmine red dye in the feces was recorded. This led to the induction of a large number of host-response genes, including inflammatory chemokines. Cold sores are caused by certain strains of the herpes simplex virus (HSV). Therefore, we further analyzed the host response by assessing immune cell recruitment to these infected tissues by flow cytometry. Laxative treatment rescued mice from lethality following genital HSV-1 infection. ; Supervision, T.L.H. Alternatively, chronic treatment with an osmotic laxative bypassed the need for an intact ENS and prevented the development of toxic megacolon and lethality. ; Software and Formal Analysis. Cell number was determined by CountBright absolute counting beads (Invitrogen). Tissues were post-fixed overnight at room temperature and then stored in 70% ethanol. Mice with megacolon (defined as a >2-fold increase in the mass of the large intestine compared to control mice) are segregated and depicted as orange dots for ease of comparison.