Das Sarma Jayasri, Iacono Kathryn, Gard Lilli, Marek Ryan, Kenyon Lawrence C, Koval Michael, Weiss Susan R
Department of Neurology, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA.
J Virol. 2008 Jun;82(11):5519-26. doi: 10.1128/JVI.01488-07. Epub 2008 Apr 2.
Some strains of mouse hepatitis virus (MHV) can induce chronic inflammatory demyelination in mice that mimics certain pathological features of multiple sclerosis. We have examined neural cell tropism of demyelinating and nondemyelinating strains of MHV in order to determine whether central nervous system (CNS) cell tropism plays a role in demyelination. Previous studies demonstrated that recombinant MHV strains, isogenic other than for the spike gene, differ in the extent of neurovirulence and the ability to induce demyelination. Here we demonstrate that these strains also differ in their abilities to infect a particular cell type(s) in the brain. Furthermore, there is a correlation between the differential localization of viral antigen in spinal cord gray matter and that in white matter during acute infection and the ability to induce demyelination later on. Viral antigen from demyelinating strains is detected initially in both gray and white matter, with subsequent localization to white matter of the spinal cord, whereas viral antigen localization of nondemyelinating strains is restricted mainly to gray matter. This observation suggests that the localization of viral antigen to white matter during the acute stage of infection is essential for the induction of chronic demyelination. Overall, these observations suggest that isogenic demyelinating and nondemyelinating strains of MHV, differing in the spike protein expressed, infect neurons and glial cells in different proportions and that differential tropism to a particular CNS cell type may play a significant role in mediating the onset and mechanisms of demyelination.
某些小鼠肝炎病毒（MHV）毒株可在小鼠中诱发慢性炎性脱髓鞘，这种脱髓鞘类似于多发性硬化的某些病理特征。我们研究了脱髓鞘和非脱髓鞘MHV毒株的神经细胞嗜性，以确定中枢神经系统（CNS）细胞嗜性是否在脱髓鞘过程中发挥作用。先前的研究表明，除刺突基因外其他基因相同的重组MHV毒株，在神经毒力程度和诱导脱髓鞘的能力方面存在差异。在此我们证明，这些毒株在感染脑内特定细胞类型的能力上也存在差异。此外，急性感染期间病毒抗原在脊髓灰质和白质中的差异定位与随后诱导脱髓鞘的能力之间存在相关性。脱髓鞘毒株的病毒抗原最初在灰质和白质中均被检测到，随后定位于脊髓白质，而非脱髓鞘毒株的病毒抗原定位主要局限于灰质。这一观察结果表明，感染急性期病毒抗原定位于白质对于诱导慢性脱髓鞘至关重要。总体而言，这些观察结果表明，表达的刺突蛋白不同的同基因脱髓鞘和非脱髓鞘MHV毒株，以不同比例感染神经元和神经胶质细胞，并且对特定CNS细胞类型的差异嗜性可能在介导脱髓鞘的起始和机制中发挥重要作用。
