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

被引:56
作者
Crotty, S
Hix, L
Sigal, LJ
Andino, R
机构
[1] Univ Calif San Francisco, Dept Microbiol & Immunol, San Francisco, CA 94143 USA
[2] Fox Chase Canc Ctr, Div Basic Sci, Philadelphia, PA 19111 USA
关键词
D O I
10.1099/0022-1317-83-7-1707
中图分类号
Q81 [生物工程学(生物技术)]; Q93 [微生物学];
学科分类号
071005 ; 0836 ; 090102 ; 100705 ;
摘要
We constructed a poliovirus receptor (PVR) transgenic mouse line carrying a PVRdelta 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.
引用
收藏
页码:1707 / 1720
页数:14
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