Herpes simplex virus type 2 transcripts in trigeminal ganglia during acute and latent infection in mice

Abstract

Adult mice were inoculated intracerebrally with herpes simplex virus type 2 (HSV-2), and perfused at days 5, 8, 81, 108, and 130 after infection. Trigeminal ganglia and roots were dissected out and embedded in paraffin. Four 35S-labelled DNA probes that contained immediate-early (ICP-0, ICP-4), delayed-early (thymidine kinase; TK), or late (morphological transforming region; MTR) genes were prepared. In situ hybridization methods or an immunoperoxidase antigen method using HSV-2 antibody were applied to serial sections. During acute infection, use of each of the 4 probes (ICP-0, ICP-4, TK, MTR) gave hybridization signals in a distribution similar to that of antigen. During latent infection, only the ICP-0 probe gave hybridization signals overlying neurons, while in adjacent sections, the other probes (ICP-4, TK, MTR) did not show signals. No antigen was detected during latency. Hybridization signals were also demonstrated in nuclei of neurons during latency using a non-radioactive ICP-0 probe labelled with a steroid hapten. These results suggest that the transcription of the HSV-2 genome is restricted during latency, with transcript localization to nuclei of neurons as has been described in latent HSV-1 infection. Evidence for latent ganglionic infection by in situ hybridization in this model is consistent with that obtained by ganglionic explantation and by reactivations induced by immunosuppression.