Wang Lulu, Dong Changyuan, Chen Dong-E, Song Zhen
Laboratory of Molecular Virus & Cancer, State Key Laboratory of Virology, Wuhan University School of Basic Medicine Wuhan 430071, China.
Department of Epidemiology and Biostatistics, Wuhan University School of Public Health Wuhan 430071, China.
Int J Clin Exp Pathol. 2014 Feb 15;7(3):890-904. eCollection 2014.
Coxsackievirus B (CVB) is a significant pathogen of neonatal diseases with severe systemic involvement and high mortality. Hence, it is essential to develop a CVB-induced acute systemic disease model on newborn mouse and study the injury at the onset phase. In this work, a clinical strain of CVB3, Nancy, and its variant strain, Macocy, were adopted in 24 hour old neonates by oral infection. The pathological changes in the heart, liver and lung tissues were analyzed by pathology assays. In situ end labeling assay for programmed cell death was carried out for liver tissues. The data on fatality and infection rates and pathology scores were analyzed statistically. The genomic sequences of the two strains were aligned. The model represented the manifest clinical syndromes of hepatitis, pneumonia and myocardial injury at the onset phase, in which massive numbers of hepatocytes had undergone programmed cell death. Statistical and pathological analysis indicated that the myocardial injury was mild, whereas the liver and lung were more severe. The fatality rate, infection and pathology of the two CVB strains were the same. Therefore, two nucleotide mutations in the 5' UTR and four amino acid mutations in polyprotein, which did not alter virulence, were shown. By peroral CVB infection of neonatal mice, we developed an acute systemic disease model for studying visceral pathology and systemic disease. At the onset of acute neonatal systemic disease, the hepatitis and pneumonia may be the dominant reason of death, as the injury of liver and lung is more severe than that of heart.
柯萨奇病毒B（CVB）是新生儿疾病的重要病原体，可导致严重的全身感染及高死亡率。因此，建立新生小鼠CVB诱导的急性全身疾病模型并研究发病初期的损伤情况至关重要。在本研究中，采用临床CVB3毒株Nancy及其变异株Macocy对24小时龄的新生小鼠进行口服感染。通过病理检测分析心脏、肝脏和肺组织的病理变化。对肝脏组织进行程序性细胞死亡的原位末端标记检测。对死亡率、感染率及病理评分数据进行统计学分析。比对两株病毒的基因组序列。该模型在发病初期表现出肝炎、肺炎及心肌损伤的明显临床综合征，其中大量肝细胞发生程序性细胞死亡。统计及病理分析表明，心肌损伤较轻，而肝脏和肺的损伤更严重。两株CVB病毒的死亡率、感染情况及病理表现相同。因此，发现5'非翻译区有两个核苷酸突变，多聚蛋白有四个氨基酸突变，但未改变病毒毒力。通过对新生小鼠进行口服CVB感染，我们建立了一个用于研究内脏病理及全身疾病的急性全身疾病模型。在急性新生儿全身疾病发病初期，肝炎和肺炎可能是主要死因，因为肝脏和肺的损伤比心脏更严重。
