Luethy Lauren N, Erickson Andrea K, Jesudhasan Palmy R, Ikizler Mine, Dermody Terence S, Pfeiffer Julie K
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.
Department of Pediatrics, Vanderbilt University School of Medicine, Nashville, TN, USA; Elizabeth B. Lamb Center for Pediatric Research, Vanderbilt University School of Medicine, Nashville, TN, USA.
Virology. 2016 Jan;487:1-10. doi: 10.1016/j.virol.2015.09.019. Epub 2015 Oct 16.
Neurotropic viruses initiate infection in peripheral tissues prior to entry into the central nervous system (CNS). However, mechanisms of dissemination are not completely understood. We used genetically marked viruses to compare dissemination of poliovirus, yellow fever virus 17D (YFV-17D), and reovirus type 3 Dearing in mice from a hind limb intramuscular inoculation site to the sciatic nerve, spinal cord, and brain. While YFV-17D likely entered the CNS via blood, poliovirus and reovirus likely entered the CNS by transport through the sciatic nerve to the spinal cord. We found that dissemination was inefficient in adult immune-competent mice for all three viruses, particularly reovirus. Dissemination of all viruses was more efficient in immune-deficient mice. Although poliovirus and reovirus both accessed the CNS by transit through the sciatic nerve, stimulation of neuronal transport by muscle damage enhanced dissemination only of poliovirus. Our results suggest that these viruses access the CNS using different pathways.
嗜神经病毒在进入中枢神经系统(CNS)之前先在周围组织中引发感染。然而,其传播机制尚未完全明确。我们使用基因标记病毒,比较了脊髓灰质炎病毒、黄热病毒17D(YFV - 17D)和3型迪尔呼肠孤病毒从后肢肌肉接种部位向小鼠坐骨神经、脊髓和脑的传播情况。虽然YFV - 17D可能通过血液进入中枢神经系统,但脊髓灰质炎病毒和呼肠孤病毒可能通过坐骨神经运输至脊髓而进入中枢神经系统。我们发现,对于这三种病毒而言,在成年免疫健全小鼠中传播效率低下,尤其是呼肠孤病毒。在免疫缺陷小鼠中,所有病毒的传播效率更高。尽管脊髓灰质炎病毒和呼肠孤病毒都通过坐骨神经进入中枢神经系统,但肌肉损伤对神经元运输的刺激仅增强了脊髓灰质炎病毒的传播。我们的结果表明,这些病毒通过不同途径进入中枢神经系统。