Attenuation of Neurovirulence, Biodistribution, and Shedding of a Poliovirus:Rhinovirus Chimera after Intrathalamic Inoculation in Macaca fascicularis
| Autor: | Karyol Poole, Sheryl Ruppel, Matthias Gromeier, Sarah K. Lawson, Christian Goetz, James O. Peggins, Robert W. Walters, Karen W. Muszynski, Elena Y. Dobrikova, James E. Estep, Steven L. Giardina, Eric M. Vela |
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| Rok vydání: | 2012 |
| Předmět: |
Rhinovirus
viruses Immunology Antibodies Viral medicine.disease_cause Microbiology Virus Cell Line Virology medicine Animals Humans Tissue Distribution Viral shedding Neutralizing antibody Virulence biology Chimera Poliovirus Virus Shedding Oncolytic virus Disease Models Animal Macaca fascicularis Cell culture Insect Science biology.protein Pathogenesis and Immunity Antibody Poliovirus Receptor Poliomyelitis |
| Zdroj: | Journal of Virology. 86:2750-2759 |
| ISSN: | 1098-5514 0022-538X |
| DOI: | 10.1128/jvi.06427-11 |
| Popis: | A dependence of poliovirus on an unorthodox translation initiation mode can be targeted selectively to drive viral protein synthesis and cytotoxicity in malignant cells. Transformed cells are naturally susceptible to poliovirus, due to widespread ectopic upregulation of the poliovirus receptor, Necl-5, in ectodermal/neuroectodermal cancers. Viral tumor cell killing and the host immunologic response it engenders produce potent, lasting antineoplastic effects in animal tumor models. Clinical application of this principle depends on unequivocal demonstration of safety in primate models for paralytic poliomyelitis. We conducted extensive dose-range-finding, toxicity, biodistribution, shedding, and neutralizing antibody studies of the prototype oncolytic poliovirus recombinant, PVS-RIPO, after intrathalamic inoculation in Macaca fascicularis . These studies suggest that intracerebral PVS-RIPO inoculation does not lead to viral propagation in the central nervous system (CNS), does not cause histopathological CNS lesions or neurological symptoms that can be attributed to the virus, is not associated with extraneural virus dissemination or replication and does not induce shedding of virus with stool. Intrathalamic PVS-RIPO inoculation induced neutralizing antibody responses against poliovirus serotype 1 in all animals studied. |
| Databáze: | OpenAIRE |
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