Poliovirus pathogenesis in a new poliovirus receptor transgenic mouse model: age-dependent paralysis and a mucosal route of infection
Poliovirus pathogenesis in a new poliovirus receptor transgenic mouse model: age-dependent paralysis and a mucosal route of infection
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DOI：
10.1099/0022-1317-83-7-1707
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发表时间：
2002-07-01
影响因子：
3.8
通讯作者：
Andino, R
中科院分区：
文献类型：
--
作者：
Crotty, S;Hix, L;Andino, R
我们构建了一个脊髓灰质炎病毒受体（PVR）转基因小鼠系，携带由β-肌动蛋白启动子驱动的PVR δ cDNA。我们将该模型称为cPVR小鼠。cPVR小鼠在多种组织（包括小肠、脑、脊髓、肌肉、血液和肝脏）中表达Pvr，并且在腹膜内、脑内或肌内接种脊髓灰质炎病毒后容易感染。腹膜内接种后，在cPVR肌肉、脑、脊髓和特别是小肠中观察到脊髓灰质炎病毒复制。cPVR小鼠在肌内感染后表现出显著的年龄依赖性麻痹，2周龄小鼠对麻痹性疾病的易感性是成年小鼠的10000倍。cPVR小鼠在鼻内感染脊髓灰质炎病毒后也容易麻痹。鼻内感染后，在嗅球、大脑、脑干和脊髓中观察到病毒复制，表明鼻内感染cPVR小鼠是球麻痹的模型。鼻内感染的小鼠经常表现出异常的神经行为。本文报道的PVR转基因小鼠为脊髓灰质炎病毒的粘膜途径感染提供了第一个可用的模型。
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.