The transgenic ICP4 promoter is activated in schwann cells in trigeminal ganglia of mice latently infected with herpes simplex virus type 1

Herpes simplex virus type 1 (HSV-1) establishes a latent infection in neuro ns of sensory ganglia, including those of the trigeminal ganglia. Latent vi ral infection has been hypothesized to be regulated by restriction of viral immediate-early gene expression in neurons. Numerous in situ hybridization studies in mice and in humans have shown that transcription from the HSV-1 genome in latently infected neurons is limited to the latency-associated t ranscripts. In other studies, immediate-early gene (ICP4) transcripts have been detected by reverse transcription-PCR (RT-PCR) in homogenates of laten tly infected trigeminal ganglia of mice. We used reporter transgenic mice c ontaining the HSV-1(F) ICP4 promoter fused to the coding sequence of the P- galactosidase gene to determine whether neurons in latently infected trigem inal ganglia activated the ICP4 promoter. Mice were inoculated via the corn eal route with HSV-1(F). At 5, 11, 23, and 37 days postinfection (dpi), tri geminal ganglia were examined for beta -galactosidase-positive cells. The n umbers of beta -galactosidase-positive neurons and nonneuronal cells were s imilar at 5 dpi. The number of positive neurons decreased at 11 dpi and ret urned to the level of mock-inoculated transgenic controls at 23 and 37 dpi. The number of positive nonneuronal cells increased at 11 and 23 dpi and re mained elevated at 37 dpi. Viral proteins were detected in neurons and nonn euronal cells in acutely infected ganglia, but were not detected in latentl y infected ganglia. Colabeling experiments confirmed that the transgenic IC P4 promoter was activated in Schwann cells during latent infection. These f indings suggest that the cells that express the HSV-1 ICP4 gene in latently infected ganglia are not neurons.