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小鼠模型中同源轮状病毒感染的分析。

Analyses of homologous rotavirus infection in the mouse model.

作者信息

Burns J W, Krishnaney A A, Vo P T, Rouse R V, Anderson L J, Greenberg H B

机构信息

Division of Gastroenterology, Palo Alto V.A. Medical Center, California 94304.

出版信息

Virology. 1995 Feb 20;207(1):143-53. doi: 10.1006/viro.1995.1060.

DOI:10.1006/viro.1995.1060
PMID:7871723
Abstract

The group A rotaviruses are significant human and veterinary pathogens in terms of morbidity, mortality, and economic loss. Despite its importance, an effective vaccine remains elusive due at least in part to our incomplete understanding of rotavirus immunity and protection. Both large and small animal model systems have been established to address these issues. One significant drawback of these models is the lack of well-characterized wild-type homologous viruses and their cell culture-adapted variants. We have characterized four strains of murine rotaviruses, EC, EHP, EL, and EW, in the infant and adult mouse model using wild-type isolates and cell culture-adapted variants of each strain. Wild-type murine rotaviruses appear to be equally infectious in infant and adult mice in terms of the intensity and duration of virus shedding following primary infection. Spread of infection to naive cagemates is seen in both age groups. Clearance of shedding following primary infection appears to correlate with the development of virus-specific intestinal IgA. Protective immunity is developed in both infant and adult mice following oral infection as demonstrated by a lack of shedding after subsequent wild-type virus challenge. Cell culture-adapted murine rotaviruses appear to be highly attenuated when administered to naive animals and do not spread efficiently to nonimmune cagemates. The availability of these wild-type and cell culture-adapted virus preparations should allow a more systematic evaluation of rotavirus infection and immunity. Furthermore, future vaccine strategies can be evaluated in the mouse model using several fully virulent homologous viruses for challenge.

摘要

就发病率、死亡率和经济损失而言,A组轮状病毒是重要的人类和兽类病原体。尽管其很重要,但有效的疫苗仍然难以实现,至少部分原因是我们对轮状病毒免疫和保护的理解不完整。已经建立了大型和小型动物模型系统来解决这些问题。这些模型的一个显著缺点是缺乏特征明确的野生型同源病毒及其细胞培养适应变体。我们在婴儿和成年小鼠模型中使用每种毒株的野生型分离株和细胞培养适应变体,对四种鼠轮状病毒毒株EC、EHP、EL和EW进行了特征分析。就初次感染后病毒排出的强度和持续时间而言,野生型鼠轮状病毒在婴儿和成年小鼠中似乎具有同等的感染性。在两个年龄组中均可见感染传播至未感染的同笼动物。初次感染后排出物的清除似乎与病毒特异性肠道IgA的产生相关。口服感染后,婴儿和成年小鼠均产生保护性免疫,这通过随后野生型病毒攻击后无排出物得以证明。当给未感染的动物接种细胞培养适应的鼠轮状病毒时,它们似乎高度减毒,并且不能有效地传播至未免疫的同笼动物。这些野生型和细胞培养适应病毒制剂的可用性应能使对轮状病毒感染和免疫进行更系统的评估。此外,未来的疫苗策略可以在小鼠模型中使用几种完全有毒力的同源病毒进行攻击来评估。

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