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Herpes simplex virus type 2 transcripts in trigeminal ganglia during acute and latent infection in mice
1Laboratory of Experimental Neuropathology, National Institute of Neurological Diseases and Stroke, NIH, Bethesda, MD 20892.
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 explanation and by reactivations induced by immunosuppression.
Insights
Herpes simplex virus type 2 (HSV-2) latency in mice involves restricted viral gene transcription, primarily ICP-0, within neuron nuclei. This suggests a conserved mechanism for HSV latency across different types.
Area of Science:
- Neurovirology
- Molecular Virology
- Infectious Diseases
Background:
- Herpes simplex virus type 2 (HSV-2) establishes lifelong latent infections, typically in sensory ganglia.
- Understanding the molecular mechanisms of HSV-2 latency is crucial for developing antiviral strategies.
Purpose of the Study:
- To investigate the transcriptional activity of the HSV-2 genome during latent infection in a mouse model.
- To determine the specific viral genes expressed during HSV-2 latency.
Main Methods:
- Adult mice were intracerebrally inoculated with HSV-2.
- Trigeminal ganglia were analyzed using in situ hybridization with DNA probes for immediate-early (ICP-0, ICP-4), delayed-early (TK), and late (MTR) genes.
- Immunoperoxidase staining was used to detect viral antigen.
Main Results:
- During acute infection, all tested HSV-2 genes (ICP-0, ICP-4, TK, MTR) showed hybridization signals and antigen expression.
- During latent infection, only the ICP-0 gene probe demonstrated hybridization signals in neuronal nuclei.
- No viral antigen was detected during latency, and other viral gene probes (ICP-4, TK, MTR) showed no signals.
Conclusions:
- HSV-2 transcription is significantly restricted during latency, with only ICP-0 expression observed in neuronal nuclei.
- This pattern of restricted transcription mirrors findings in latent herpes simplex virus type 1 (HSV-1) infection.
- In situ hybridization provides evidence for latent ganglionic infection by HSV-2.