title: Poliovirus pathogenesis in a new poliovirus receptor transgenic mouse model: age-dependent paralysis and a mucosal route of infection.
abstract: We constructed a poliovirus receptor (PVR) transgenic mouse line carrying a PVR delta cDNA driven by a beta-actin promoter. We refer to this model as the cPVR mouse. The cPVR mice express Pvr in a variety of tissues (including small intestines, brain, spinal cord, muscle, blood and liver) and are susceptible to infection after intraperitoneal, intracerebral or intramuscular inoculation of poliovirus. After intraperitoneal inoculation, poliovirus replication is observed in cPVR muscle, brain, spinal cord and, notably, small intestine. The cPVR mice exhibit a striking age-dependent paralysis after intramuscular infection, with 2-week-old mice being 10,000-fold more susceptible to paralytic disease than adult mice. The cPVR mice are also susceptible to paralysis following intranasal infection with poliovirus. After intranasal infection, virus replication is observed in the olfactory bulb, cerebrum, brain stem and spinal cord, suggesting that intranasal infection of cPVR mice is a model for bulbar paralysis. Intranasally infected mice frequently display unusual neurological behaviours. The PVR transgenic mouse reported here provides the first available model for a mucosal route of infection with poliovirus.
authors.affiliation: Department of Microbiology and Immunology, University of California, Box 0414, San Francisco, CA 94143, USA1.
authors.forename: Shane
authors.initials: S
authors.lastname: Crotty
authors.affiliation: Department of Microbiology and Immunology, University of California, Box 0414, San Francisco, CA 94143, USA1.
authors.forename: Laura
authors.initials: L
authors.lastname: Hix
authors.affiliation: Basic Science Division, Fox Chase Cancer Center, Philadelphia, PA 19111, USA2.
authors.forename: Luis J
authors.initials: LJ
authors.lastname: Sigal
authors.affiliation: Department of Microbiology and Immunology, University of California, Box 0414, San Francisco, CA 94143, USA1.
authors.forename: Raul
authors.initials: R
authors.lastname: Andino
mesh_terms: D000367:Age Factors; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000821:virology; D004195:Disease Models, Animal; D007421:Intestine, Small / Q000378:metabolism / Q000821:virology; D008099:Liver / Q000378:metabolism; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009132:Muscles / Q000378:metabolism / Q000821:virology; D009928:Organ Specificity; D010243:Paralysis / Q000209:etiology / Q000821:virology; D011051:Poliomyelitis / Q000097:blood / Q000503:physiopathology / Q000821:virology*; D017955:Poliovirus / Q000235:genetics / Q000472:pathogenicity / Q000502:physiology; D011055:Poliovirus Vaccine, Oral / Q000009:adverse effects; D012333:RNA, Messenger / Q000032:analysis; D012367:RNA, Viral / Q000235:genetics; D011991:Receptors, Virus / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism / Q000821:virology; D014779:Virus Replication
chemical_list: D008565:Membrane Proteins; D011055:Poliovirus Vaccine, Oral; D012333:RNA, Messenger; D012367:RNA, Viral; D011991:Receptors, Virus; C066100:poliovirus receptor