Molecular pathogenesis of type 2 poliovirus in mice
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T Couderc1, B Guinguene, F Horaud
1Unité de Virologie Médicale, Institut Pasteur, Paris, France.
Abstract:
Lansing strain of poliovirus type 2 (PV-2) produces a fatal paralytic disease in mice after intracerebral inoculation. To identify virus-containing nerve cells in poliovirus-infected mice, we developed a technique of in situ hybridization for viral RNA with a poliovirus-specific riboprobe. Large numbers of genomes were found in motoneurons and their processes, as well as in ghosts of neurons with or without inflammatory cells. This indicates that the death of motoneurons is due to a direct effect of viral replication. The presence of viral RNA in neuronal processes suggests an axonal dissemination of poliovirus within the central nervous system (CNS). Detection of viral genomes in small cells located in anterior and in posterior horns shows that motoneurons are not the only cells susceptible to poliovirus in the CNS. To see if PV-2/Lansing still exits in nature, PV-2 isolated from the CNS and from the gut of two human cases of paralytic poliomyelitis were characterized by determining epitope maps and phenotypic markers and by sequencing regions of the genome coding for antigenic sites and the 5' non-coding region. Comparison of virus isolated from the intestine and from the CNS of the same subject revealed a high degree of homology, suggesting that virus isolated from the gut is representative of virus in the neuronal lesions. The isolate from a case had more homology to PV-2/Lansing, whereas the other isolate showed more homology to PV-2/Sabin. These results show that, despite intensive vaccination with oral polio vaccine for 25 years, wild PV-2/Lansing-like viruses, pathogenic for mice, still circulate in nature ad induce human paralytic cases.
Insights
Poliovirus type 2 (PV-2) directly infects and kills nerve cells in mice, spreading through axons. Wild PV-2 strains, despite vaccination, still circulate and cause paralytic polio in humans.
Area of Science:
- Neurovirology
- Molecular Virology
- Infectious Diseases
Background:
- The Lansing strain of poliovirus type 2 (PV-2) causes fatal paralytic disease in mice.
- Understanding poliovirus tropism and spread within the central nervous system (CNS) is crucial for disease control.
Purpose of the Study:
- To identify virus-containing nerve cells in poliovirus-infected mice using in situ hybridization.
- To investigate the continued circulation and characteristics of wild PV-2 strains in humans despite vaccination efforts.
Main Methods:
- In situ hybridization with a poliovirus-specific riboprobe to detect viral RNA in mouse CNS.
- Epitope mapping, phenotypic marker analysis, and genomic sequencing of PV-2 isolates from human cases.
Main Results:
- PV-2 RNA was abundant in motoneurons and their processes, indicating direct viral replication and axonal spread within the CNS.
- Viral genomes were also detected in other neuronal cell types, suggesting broader susceptibility.
- PV-2 isolates from human cases showed homology to both PV-2/Lansing and PV-2/Sabin, with gut and CNS isolates being highly similar within individuals.
Conclusions:
- Motoneuron death in PV-2 infected mice is a direct result of viral replication.
- Axonal dissemination contributes to poliovirus spread within the CNS.
- Wild PV-2 strains, including pathogenic Lansing-like viruses, persist in circulation and cause human paralytic poliomyelitis, underscoring the need for continued surveillance and vaccination.