Sun N, Perlman S
Department of Pediatrics, University of Iowa, Iowa City 52242.
J Virol. 1995 Feb;69(2):633-41. doi: 10.1128/JVI.69.2.633-641.1995.
Mouse hepatitis virus strain JHM (MHV-JHM) causes a chronic encephalomyelitis in susceptible mice, with histological evidence of demyelination in the spinal cord. After intranasal inoculation, virus spreads retrogradely to several brain structures along neuroanatomic projections to the main olfactory bulb. In the absence of experimental intervention, mice become moribund before the spinal cord is infected. In this study, infusions of anti-MHV neutralizing monoclonal antibodies were administered to protect mice from the MHV-JHM-induced acute encephalitis and to allow survival until virus spread to the spinal cord. Under these conditions, virus was observed to enter specific layers (primarily laminae V to VII) in the gray matter of the upper spinal cord, consistent with transneuronal spread. While the brain structures which are the sources for virus spread to the spinal cord cannot be determined with certainty, the ventral reticular nucleus is likely to be important since it is consistently and extensively labeled in all mice and receives projections from subsequently infected areas of the spinal cord. After initial entry into the gray matter, virus rapidly spread to the white matter of the spinal cord. During the early stages of this process, extensive infection of astrocytes was noted, suggesting that cell-to-cell spread via these glial cells is an important part of this process. Reports from other laboratories using cultured cells strongly suggested that astrocytes serve as important regulators of oligodendrocyte function and, by extrapolation, have a major role in vivo in the processes of both demyelination and remyelination. Thus, our results not only outline the probable pathway used by MHV-JHM to infect the white matter of the spinal cord but also, with the assumption that infection of astrocytes leads to subsequent dysfunction, raise the possibility that infection of these cells contributes to the demyelinating process.
小鼠肝炎病毒JHM株（MHV-JHM）可在易感小鼠中引发慢性脑脊髓炎，脊髓有脱髓鞘的组织学证据。经鼻内接种后，病毒沿神经解剖投射逆行扩散至几个脑结构，到达主嗅球。在没有实验干预的情况下，小鼠在脊髓被感染之前就会濒死。在本研究中，给予抗MHV中和单克隆抗体输注，以保护小鼠免受MHV-JHM诱导的急性脑炎，并使其存活至病毒扩散到脊髓。在这些条件下，观察到病毒进入脊髓上部灰质的特定层（主要是V至VII层），这与跨神经元传播一致。虽然无法确定病毒扩散到脊髓的脑结构来源，但腹侧网状核可能很重要，因为它在所有小鼠中都持续且广泛地被标记，并接受来自脊髓后续感染区域的投射。病毒最初进入灰质后，迅速扩散到脊髓白质。在此过程的早期阶段，观察到星形胶质细胞广泛感染，这表明通过这些神经胶质细胞的细胞间传播是该过程的重要组成部分。其他实验室使用培养细胞的报告强烈表明，星形胶质细胞是少突胶质细胞功能的重要调节因子，由此推断，其在体内脱髓鞘和再髓鞘形成过程中起主要作用。因此，我们的结果不仅概述了MHV-JHM感染脊髓白质可能使用的途径，而且在假设星形胶质细胞感染导致随后功能障碍的情况下，增加了这些细胞感染促成脱髓鞘过程的可能性。
