A nonpolio enterovirus with respiratory tropism causes poliomyelitis in intercellular adhesion molecule 1 transgenic mice
A nonpolio enterovirus with respiratory tropism causes poliomyelitis in intercellular adhesion molecule 1 transgenic mice
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DOI：
10.1073/pnas.0403998101
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发表时间：
2004-09-14
影响因子：
11.1
通讯作者：
Gromeier, M
中科院分区：
文献类型：
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作者：
Dufresne, AT;Gromeier, M
柯萨奇病毒A21(CoxsackieVirus A21，CAV21)属于微小核糖核酸病毒属肠道病毒属中的人类肠道病毒C(Human EnterVirus C，HEV-C)。HEV-C与脊髓灰质炎病毒(PV)有惊人的同源性，后者是肠道病毒中最接近的亲缘关系。尽管CAV21和PV具有很高的序列同源性，但由于它们对宿主受体的不同使用，它们会引起不同的临床疾病。PV导致脊髓灰质炎，而CAV21有共同的受体和导致上呼吸道感染主要组鼻病毒的倾向。作为CAV21感染的模型，我们开发了表达人细胞间黏附分子1的转基因小鼠，人细胞间黏附分子1是CAV21的细胞表面受体。令人惊讶的是，通过肌肉注射途径给这些小鼠注射CAV21会导致一种与脊髓灰质炎一致的瘫痪情况。病毒似乎通过逆行轴突运输入侵中枢神经系统，这已被证明发生在类似的PV感染中。我们检测到人类细胞间黏附分子1在转基因小鼠和人类脊髓前角运动神经元上的表达，表明HEV-C成员可能与PV一样具有在人类引发脊髓灰质炎的潜力。
Coxsackievirus A21 (CAV21) is classified within the species Human enterovirus C (HEV-C) of the Enterovirus genus of picornaviruses. HEV-C share striking homology with the polioviruses (PV), their closest kin among the enteroviruses. Despite a high level of sequence identity, CAV21 and PV cause distinct clinical disease typically attributed to their differential use of host receptors. PV cause poliomyelitis, whereas CAV21 shares a receptor and a propensity to cause upper respiratory tract infections with the major group rhinoviruses. As a model for CAV21 infection, we have developed transgenic mice that express human intercellular adhesion molecule 1, the cell-surface receptor for CAV21. Surprisingly, CAV21 administered to these mice via the intramuscular route causes a paralytic condition consistent with poliomyelitis. The virus appears to invade the CNS by retrograde axonal transport, as has been demonstrated to occur in analogous PV infections. We detected human intercellular adhesion molecule 1 expression on both transgenic mouse and human spinal cord anterior horn motor neurons, indicating that members of HEV-C may share PV's potential to elicit poliomyelitis in humans.