Houtman J J, Fleming J O
Department of Medical Microbiology and Immunology, University of Wisconsin, Madison 53706, USA.
J Neurovirol. 1996 Apr;2(2):101-10. doi: 10.3109/13550289609146543.
Infection of rodents with murine coronavirus JHM results in a subacute or chronic demyelinating disease which serves as a model for the human disease multiple sclerosis. Previous studies with JHMV have established a role for the immune system in both viral clearance and demyelination. To further clarify the role of the immune system in JHMV pathogenesis, several strains of congenitally immunodeficient mice were studied. Infection of immunocompetent C57BL/6 mice with JHMV resulted in severe paralysis and demyelination and complete clearance of infectious virus from the brain (C+D+ phenotype). In contrast, infected SCID mice showed little or no paralysis or demyelination and were unable to clear infectious virus (C-D- phenotype). Athymic nude mice and a proportion of mice lacking MHC Class I or II expression exhibited robust demyelination but did not completely clear infectious virus from the brain (C-D+ phenotype). These results are consistent with an immune-mediated mechanism for JHMV-induced demyelination, but indicate that the immune mechanisms which participate in demyelination and viral clearance are distinct. It may thus be possible to experimentally alter immunopathological responses without impairing antimicrobial immunity.
用鼠冠状病毒JHM感染啮齿动物会导致一种亚急性或慢性脱髓鞘疾病，该疾病可作为人类多发性硬化症的模型。先前对JHMV的研究已确定免疫系统在病毒清除和脱髓鞘过程中均发挥作用。为了进一步阐明免疫系统在JHMV发病机制中的作用，对几种先天性免疫缺陷小鼠品系进行了研究。用JHMV感染具有免疫能力的C57BL/6小鼠会导致严重麻痹和脱髓鞘，并使传染性病毒从脑中完全清除（C+D+表型）。相比之下，感染的SCID小鼠几乎没有或没有出现麻痹或脱髓鞘现象，并且无法清除传染性病毒（C-D-表型）。无胸腺裸鼠以及一部分缺乏MHC I类或II类表达的小鼠表现出强烈的脱髓鞘，但并未从脑中完全清除传染性病毒（C-D+表型）。这些结果与JHMV诱导脱髓鞘的免疫介导机制一致，但表明参与脱髓鞘和病毒清除的免疫机制是不同的。因此，有可能在不损害抗菌免疫的情况下通过实验改变免疫病理反应。
