Murine nasal-associated lymphoid tissue (NALT) harbors human alphaherpesvirus 1 (HSV-1) DNA during latency, and dexamethasone triggers viral replication

Human alphaherpesvirus 1 (HSV-1) acute infection causes various diseases, including herpes esophagitis. HSV-1 subsequently establishes lifelong latency in neurons within the trigeminal ganglia and central nervous system. Viral DNA, but not infectious virus, was consistently detected in nasopharyngeal lymphoid tissue (NALT) of latently infected mice. NALT is structurally and functionally comparable with the tonsils of other mammals, including humans. RNA and protein expression of infected cell protein 0 (ICP0) and ICP4 plus virus production were consistently detected when NALT explants were cultured with a medium containing dexamethasone, a synthetic corticosteroid. Sorting NALT cells from HSV-1 latently infected mice revealed dendritic cells, microfold cells, and natural killer cells that harbor HSV-1 DNA. Virus shedding was readily detected when viral DNA-positive NALT cells were cultured in a medium containing dexamethasone. These studies revealed that specific NALT cells harbor viral DNA, and dexamethasone triggered viral replication and virus production, suggesting that reactivation from a latent or quiescent infection had occurred.