Ciarlet M, Gilger M A, Barone C, McArthur M, Estes M K, Conner M E
Division of Molecular Virology, Baylor College of Medicine, Houston, Texas, 77030, USA.
Virology. 1998 Nov 25;251(2):343-60. doi: 10.1006/viro.1998.9406.
The rabbit model of rotavirus infection has proved to be useful for assessing active immunity and protection after infection or vaccination with virus or virus-like particles. One limitation of the rabbit model is that after experimental infection of rabbits, clinical diarrhea is not routinely induced. Lack of diarrhea in the rabbit model has been proposed to be due to the fluid absorptive capability of the cecum or attenuation of virus strains through tissue culture adaptation. To test whether a wild-type lapine rotavirus strain BAP (BAPwt) isolated from diarrheic rabbits would cause disease on passage in rabbits, 1-, 2-, 10-, and 16-week-old rabbits were orally inoculated with BAPwt, its tissue culture-adapted counterpart strain (BAP-2), tissue culture-adapted lapine strain ALA, or PBS. Lapine rotavirus infection in 1-week-old, but not >/=2-week-old, rabbits resulted in the development of disease characterized by soft, wet, yellow-to-brownish-green partially formed-to-liquid stools observed only at the time of virus antigen shedding. The level and duration of virus shedding after infection were prolonged in 1-week-old rabbits compared with rabbits >/=2 weeks of age. Although diarrhea was not observed beyond the first 2 weeks of life, histopathological changes, including villus shortening and fusion, increased vacuolation of epithelial cells, and mononuclear infiltration of the lamina propria, were observed throughout the small intestine between 12 and 120 h after ALA infection in 1-week-old, 1- to 2-month-old, and 11-month-old rabbits. In 11-month-old rabbits, onset of intestinal damage appeared to be slightly delayed, was less severe, and was not observed in the duodenum. There were no differences in the immune responses to rotavirus infection in rabbits of different age groups (1 week to 5 years of age). All lapine rotavirus-inoculated rabbits seroconverted and were protected from virus challenge at 28 days postinoculation. Like in mice, rotavirus disease is age restricted in rabbits.
轮状病毒感染的兔子模型已被证明可用于评估感染病毒或病毒样颗粒或接种疫苗后的主动免疫和保护作用。兔子模型的一个局限性在于,对兔子进行实验性感染后,通常不会引发临床腹泻。有人提出兔子模型中缺乏腹泻是由于盲肠的液体吸收能力或病毒株通过组织培养适应而发生减毒。为了测试从腹泻兔子中分离出的野生型兔轮状病毒株BAP(BAPwt)在兔子传代后是否会引发疾病,对1周龄、2周龄、10周龄和16周龄的兔子口服接种BAPwt、其组织培养适应对应株(BAP-2)、组织培养适应兔株ALA或PBS。1周龄而非≥2周龄的兔子感染兔轮状病毒后会引发疾病,其特征为仅在病毒抗原排出时观察到软的、湿的、黄色至棕绿色部分成形至液体状粪便。与≥2周龄的兔子相比,1周龄兔子感染后病毒排出的水平和持续时间延长。尽管在出生后的前2周之后未观察到腹泻,但在1周龄、1至2月龄和11月龄兔子感染ALA后12至120小时内,在整个小肠中均观察到组织病理学变化,包括绒毛缩短和融合、上皮细胞空泡化增加以及固有层单核细胞浸润。在11月龄兔子中,肠道损伤的发生似乎略有延迟,程度较轻,且在十二指肠中未观察到。不同年龄组(1周龄至5岁)的兔子对轮状病毒感染的免疫反应没有差异。所有接种兔轮状病毒的兔子均发生血清转化,并在接种后28天免受病毒攻击。与小鼠一样,轮状病毒疾病在兔子中也受年龄限制。