Summary auto-generated
This study examined how herpes simplex virus type 1 (HSV-1) is cleared from the peripheral nervous system of C57BL/10 mice following experimental infection. Researchers infected mice by inoculating virulent HSV-1 strain SC16 onto flank skin and tracked viral presence in spinal ganglia and nerve tissue. Viral DNA and antigens accumulated in sensory neurons until 136 hours post-infection, then underwent remarkably rapid clearance, with virtually complete disappearance of detectable viral antigens within 8 hours. The clearance correlated with CD8+ T-cell activity and did not depend on neuron destruction, consistent with a non-cytolytic immune response. An unexpected finding was the continued presence of viral antigens in sensory nerve axons for at least 8 hours after disappearing from neuronal cell bodies. This suggests viral proteins may be transported along axons toward peripheral nerve terminals after active infection ceases, raising intriguing questions about virus movement during the resolution phase and potential implications for skin lesion development.
Key findings
- HSV-1 infection in sensory neurons peaked at 136 hours post-inoculation, followed by precipitous clearance of viral antigens within 8-16 hours.
- Viral antigen disappearance correlated with HSV DNA clearance and did not require neuronal destruction, confirming a non-cytolytic CD8+ T-cell mediated response.
- Viral antigens persisted in sensory nerve axons for at least 8 hours after disappearing from neuronal cell bodies, suggesting anterograde transport of viral proteins along axons.
- Schwann cells were transiently infected with HSV-1 but satellite glia were rarely infected during this infection model.
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Abstract
Clearance of herpes simplex virus (HSV) from spinal ganglia of experimentally infected mice is known to be dependent on CD8+ T-cells but not on destruction of infected neurons, consistent with a non- cytolytic Tc2 response in the peripheral nervous system. Here, we demonstrate the striking rapidity of such a response in C57BL/10 mice. The number of neurons containing viral DNA and viral antigens increased until 136 h after inoculation of virulent HSV type 1 (strain SC16) into flank skin. Subsequent disappearance of HSV DNA and antigens from infected ganglia was virtually complete only 8 h later. A consistent and unexpected observation was detection of viral antigens in sensory nerve axons for at least 8 h after their disappearance from neuronal somas, raising the intriguing possibility that virus or viral proteins may be transported distally after infection has been terminated.