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Journal of General Virology (2002), 83, 1707-1720.
© 2002 Society for General Microbiology

Animal: RNA Viruses

Poliovirus pathogenesis in a new poliovirus receptor transgenic mouse model: age-dependent paralysis and a mucosal route of infection

Shane Crottya,1, Laura Hix1, Luis J. Sigal2 and Raul Andino1

Department of Microbiology and Immunology, University of California, Box 0414, San Francisco, CA 94143, USA1
Basic Science Division, Fox Chase Cancer Center, Philadelphia, PA 19111, USA2

Author for correspondence: Raul Andino. Fax +1 415 476 0939. e-mail andino{at}itsa.ucsf.edu

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 10000-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.




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