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Pathogenesis of human poliovirus infection in mice. I. Clinical and pathological studies
Abstract:
Human poliovirus infection in mice was studied to determine the similarities to human poliomyelitis, the selective vulnerability of neurons to infection, the role of the immune response in age-dependent susceptibility, and possible viral persistence. Mice inoculated intracerebrally (ic) with the Lansing type 2 poliovirus developed a disease with clinical, pathological, and age-dependent features resembling human poliomyelitis. Adult mice had a shorter incubation period (50% paralysis, Day 8 vs. Day 13) and a higher incidence of paralysis (97% vs. 79%) than newborns. Only paralyzed animals had pathologic changes in the spinal cord, and these corresponded to the degree of paralysis. Fluorescent antibody staining showed that selective infection of neurons was most intense in the anterior horn motor neurons of the spinal cord. There was no extraneural virus replication and no systemic neutralizing antibody response. Cyclophosphamide immunosuppression enhanced rather than diminished disease, indicating that maturation of immune responses did not explain the relative resistance of newborns to paralysis.
Insights
Poliovirus infection in mice mimics human polio, with adult mice showing greater susceptibility. Newborn mice are relatively resistant, and immune responses do not explain this age-dependent difference in poliovirus disease.
Area of Science:
- Neuroscience
- Virology
- Immunology
Background:
- Poliovirus causes poliomyelitis, a serious neurological disease.
- Understanding poliovirus infection in animal models is crucial for studying human disease.
- Age-dependent susceptibility and immune response roles require further investigation.
Purpose of the Study:
- To investigate poliovirus infection similarities in mice and humans.
- To determine neuron vulnerability and age-dependent susceptibility.
- To explore the role of the immune response and viral persistence.
Main Methods:
- Intracerebral inoculation of Lansing type 2 poliovirus in mice.
- Clinical observation for paralysis and incubation period.
- Pathological examination of spinal cord tissue.
- Fluorescent antibody staining for viral localization.
- Immunosuppression using cyclophosphamide.
Main Results:
- Mouse model exhibited clinical and pathological features of human poliomyelitis.
- Adult mice showed increased susceptibility (shorter incubation, higher paralysis incidence) compared to newborns.
- Selective infection of anterior horn motor neurons was observed.
- No extraneural virus replication or systemic antibody response detected.
- Immunosuppression paradoxically enhanced disease severity.
Conclusions:
- Mouse model effectively replicates key aspects of human poliovirus infection.
- Age-dependent susceptibility is not solely explained by immune maturation.
- Anterior horn motor neurons are primary targets for poliovirus infection in this model.
- Further research is needed to elucidate the mechanisms of age-dependent resistance.