Ciarlet Max, Conner Margaret E, Finegold Milton J, Estes Mary K
Department of Molecular Virology & Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.
J Virol. 2002 Jan;76(1):41-57. doi: 10.1128/jvi.76.1.41-57.2002.
Group A rotaviruses are major pathogens causing acute gastroenteritis in children and animals. To determine if group A rotavirus replicates and induces disease in rats, antibody-negative Lewis neonatal or adult rats were inoculated orally with tissue culture-adapted human (Wa, WI61, and HAL1166), simian (rhesus rotavirus [RRV] and SA11), bovine (WC3), lapine (ALA), or porcine (OSU) rotavirus strains, wild-type murine (EC(wt)) rotavirus strain, or phosphate-buffered saline (PBS). Rotavirus infection in rats was evaluated by (i) clinical findings, (ii) virus antigen shedding or infectious virus titers in the feces or intestinal contents measured by enzyme-linked immunosorbent assay or fluorescent-focus assay, (iii) histopathological changes in the small intestine, (iv) distribution of rotavirus antigen in small-intestine sections by immunofluorescence, and (v) growth rate. Rotavirus infection of 5-day-old but not > or =21-day-old rats resulted in diarrhea that lasted from 1 to 10 days postinoculation. The severity of disease and spread of infection to naIve littermates differed depending on the virus strain used for inoculation. The duration of virus antigen shedding following infection was considerably prolonged (up to 10 days) in neonatal rats compared to that in 21-day-old rats (1 or 2 days). Based on lack of virus antigen shedding and disease induction, the murine EC(wt) rotavirus was the only strain tested that did not infect rats. Histopathological changes in the small-intestine mucosa of 5-day-old RRV-inoculated rats but not of PBS-inoculated rats was limited to extensive enterocyte vacuolation in the ileum. In RRV-inoculated neonatal rats, rotavirus antigen was detected in the epithelial cells on the upper half of the intestinal villi of the jejunum and ileum. In addition, infection of neonatal rats with RRV but not with PBS resulted in reduced weight gain. Rats infected with group A rotaviruses provide a new animal model with unique features amenable to investigate rotavirus pathogenesis and the molecular mechanisms of intestinal development, including physiological factors that may regulate age-dependent rotavirus-induced diarrhea.
A组轮状病毒是导致儿童和动物急性胃肠炎的主要病原体。为了确定A组轮状病毒是否能在大鼠体内复制并引发疾病，将抗体阴性的新生或成年Lewis大鼠经口接种组织培养适应的人源（Wa、WI61和HAL1166）、猴源（恒河猴轮状病毒[RRV]和SA11）、牛源（WC3）、兔源（ALA）或猪源（OSU）轮状病毒株、野生型鼠源（EC(wt)）轮状病毒株或磷酸盐缓冲盐水（PBS）。通过以下方法评估大鼠的轮状病毒感染情况：（i）临床症状；（ii）用酶联免疫吸附测定或荧光焦点测定法测量粪便或肠内容物中的病毒抗原释放或感染性病毒滴度；（iii）小肠的组织病理学变化；（iv）通过免疫荧光法检测小肠切片中轮状病毒抗原的分布；（v）生长速率。5日龄而非≥21日龄的大鼠感染轮状病毒后会出现腹泻，腹泻持续时间为接种后1至10天。疾病的严重程度以及感染向未感染同窝幼仔的传播情况因用于接种的病毒株而异。与21日龄大鼠（1或2天）相比，新生大鼠感染后病毒抗原释放的持续时间显著延长（长达10天）。基于缺乏病毒抗原释放和疾病诱导，鼠源EC(wt)轮状病毒是所测试的唯一未感染大鼠的毒株。接种RRV的5日龄大鼠而非接种PBS的大鼠小肠黏膜的组织病理学变化仅限于回肠广泛的肠细胞空泡化。在接种RRV的新生大鼠中，在空肠和回肠肠绒毛上半部分的上皮细胞中检测到轮状病毒抗原。此外，新生大鼠感染RRV而非PBS会导致体重增加减少。感染A组轮状病毒的大鼠提供了一种新的动物模型，具有独特的特征，适合用于研究轮状病毒发病机制以及肠道发育的分子机制，包括可能调节年龄依赖性轮状病毒诱导腹泻的生理因素。
