BALB/c小鼠在HSV-1不同条件感染下的临床与病理及病原差异分析

Differences in clinical, pathological and etiological features of herpes simplex virus 1 infection in different BALB/c mouse models

目的探讨BALB/c小鼠模型在不同条件下感染HSV-1后的临床表现、病理现象及组织器官中的病毒分布特性，为HSV-1不同毒株感染模式小鼠的研究提供综合的参考指标体系。方法本研究利用HSV-1 17＋和McKrae毒株，经滴鼻和角膜途径感染不同周龄的BALB/c小鼠，建立急性感染模式；经皮下和足垫途径感染不同周龄的BALB/c小鼠，建立慢性感染模式。结果实验小鼠的临床、病理学、病原学指标的观察结果表明：虽然小鼠临床症状均表现为倒毛、弓背，但在不同条件下感染不同毒株的动物其体重和死亡率指标存在差异；定量PCR技术检测结果证实神经组织（脑、脊髓、三叉）内病毒载量的增殖趋势不同；病理学检查提示急性感染组仅脑组织中出现明显病理损伤，慢性感染组仅三叉神经中表现病理损伤。而慢性感染组动物的三叉神经组织，虽未检测到具有指标意义的潜伏相关转录本（latency associated transcript, LAT），但是其组织块与Vero细胞共培养却可导致细胞出现感染性病变。结论HSV-1不同毒株经不同攻毒途径感染小鼠后，小鼠在体重、死亡率，毒株在机体内的复制模式等方面存在明显差异。因此，基于不同感染模式的相关研究，其观察指标侧重点应该不同。

Objective To provide a comprehensive reference index for different mouse models of herpes simplex virus 1 （ HSV-1） infection by investigating the related clinical manifestations, pathological features and characteristics of viral distribution in tissues and organs of BALB/c mice infected with different HSV-I strains by using different strategies. Methods Acute infection models were established by challenging BALB/c mice at age three or six weeks with HSV-1 17＋ and McKrae strains via intranasal and corneal administrations. Correspondingly, chronic infection models were established with BALB/c mice through sub- cutaneous and foot pad injections. Results Although all experimental mice showed trichiasis and roach- back, there were differences in weight and fatality rate among different groups. Results of the quantitative PCR detection indicated that the proliferation of HSV-1 in the nervous tissues （brain, spinal cord, trigeminal ganglion） varied among different groups. The pathological examination indicated that in the acute infection groups, significant pathological changes only occurred in the brain tissues, while in the chronic infection groups, pathological injuries only occurred in the trigeminal ganglia. Although a key index latency-associated transcript （LAT） was not detected in the trigemiual nerve tissues of mice in the chronic infection groups, co- culturing the tissues with Vero cells resulted in infectious lesions in the cells. Conclusion This study indi- cates that there are significant differences in weight and fatality rate among different BALB/c mouse models of HSV-1 infection. Varied replication dynamics of HSV-1 were observed in different tissues or organs of the BALB/c mice in different groups. Therefore, different indexes should be adopted to evaluate different HSV- 1 infection models.