Pathogenesis of spongiform encephalopathy induced by viral infection

小鼠肝炎病毒（MHV）是冠状病毒家族的一员。刺突蛋白（S）由病毒颗粒突起组成，负责与受体结合，也负责MHV的细胞进入机制。从MHV的高度神经致病性JHM株cl-2分离的可溶性受体抗性突变体7（srr 7）与其母体病毒相比显示出轻微降低的毒力，在接种后（pi）48小时诱导海绵状变性，在脑室周围区域中具有病毒抗原表达。在srr 7感染的过程中，在pi 2天出现小的海绵状病变，并且这些扩散到感染后8至10天形成海绵状脑病。在这项研究中，我们注意到srr 7的神经毒力随着培养时间的缩短而增加，在某些情况下，表现出神经元的感染性，与l-2感染的观察结果相似。通过对srr 7基因的重克隆，我们获得了几个S蛋白区发生单或双氨基酸突变的突变株，这些突变株均表现出MHVR非依赖性感染性。各突变体病毒对脑实质的侵袭方式不同，这可能与病毒感染后对脑内细胞外基质的亲和力不同有关，为阐明脑海绵变性的机制提供了新的范例。

Mouse hepatitis virus (MHV) is a member of the coronavirus family. Spike (S) protein, composed of virion projections, is responsible for binding to a receptor and also for the cell entry mechanism of MHV. Soluble receptor-resistant mutant 7 (srr7) isolated from the highly neuropathogenic JHM strain of MHV, cl-2, shows slightly reduced virulence compared to its maternal virus, inducing spongiotic degeneration at 48 hours post-inoculation (pi) with viral antigens-expression in the periventricular areas.During the course of infection with srr7, small spongiotic lesions appear at 2 days pi,and these spread out to form spongiform encephalopathy by 8 to 10 days pi. In thisstudy, we noted that the neurovirulence of srr7 increases with a shorter incubationperiod, and, in some cases, exhibits infectivity of neurons, similar to the observation incl-2 infection. Through the re-cloning of srr7, we obtained several mutants with singleor double substitutions of amino acids in the S protein rei on. All of these mutantviruses exhibited major MHV receptor (MHVR)-independent infectivity due to themutation of the S-coding region, which was examined by in vitro expression of thegenes. Each mutant virus showed different pattern of invasion into the brainparenchyma, provably due to the difference in the affinity to extracellular matrixemerged after the infection in the brain, which provides a new paradigm to elucidatethe mechanisms of spongiotic degeneration in the brain.