Estes M K, Morris A P
Division of Molecular Virology, Baylor College of Medicine, Houston, Texas 77030, USA.
Adv Exp Med Biol. 1999;473:73-82.
Acute infectious gastroenteritis is a major cause of infant morbidity in developed countries and of infant mortality in developing areas of the world. Rotavirus is recognized as the most important etiologic agent of infantile gastroenteritis, and studies of rotavirus serve as models to understand the complex interactions between enteric viruses and the multifunctional cells of the gastrointestinal tract. Understanding such interactions is significant for microbial pathogenesis because most (> 80%) infections are initiated at mucosal surfaces. Rotaviruses are pathogens that infect the mature enterocytes of the villi in the intestine and infection appears to be limited to these highly differentiated cells in immunologically competent hosts. In such hosts, infections are generally acute yet diarrheal disease can be severe and life-threatening. Disease generally is resolved within 2-5 days after infection if affected hosts receive adequate rehydration. In immunocompromised hosts, virus infections persist, virus can be detected extraintestinally and virus excretion may be detected for extended periods of time (many months). Rotaviruses infect almost all mammalian and some avian species and much of our understanding of rotavirus pathogenesis has come from studies in animal models, particularly in small animal models (mice and rabbits), but also in larger animals (cows and piglets). Studies in children are limited due to the difficulty and lack of clinical need of obtaining biopsies from infants and the inability to determine the precise time of natural infections. In all animal species where naïve animals can be infected, disease is age-dependent; for example, in mice and rabbits, diarrheal disease is the outcome of infections that occur only during the first two weeks of life (Ciarlet et al., 1998; Starkey et al., 1986; Ramig 1988; Ward et al., 1990; Burns et al., 1995), while animals remain susceptible to viral infection into adulthood. Rotavirus infections have been reported to occur repeatedly in humans from birth to old age, but the majority of infections after the first 2 years of life are asymptomatic or associated with mild gastrointestinal symptoms. The age-related resistance to rotavirus-induced diarrhea in humans is thought to be mediated primarily by acquired immunity, but it is not possible to directly test if humans also exhibit an age-dependent resistance to disease based on other factors such as intestinal development and maturation. Currently, our best understanding of the mechanisms of rotavirus pathogenesis rely on results obtained in animal models.
急性感染性肠胃炎是发达国家婴幼儿发病的主要原因，也是世界上发展中地区婴幼儿死亡的主要原因。轮状病毒被认为是婴幼儿肠胃炎最重要的病原体，对轮状病毒的研究可作为了解肠道病毒与胃肠道多功能细胞之间复杂相互作用的模型。了解此类相互作用对微生物发病机制具有重要意义，因为大多数（>80%）感染始于黏膜表面。轮状病毒是感染肠道绒毛成熟肠上皮细胞的病原体，在免疫功能正常的宿主中，感染似乎仅限于这些高度分化的细胞。在这类宿主中，感染通常为急性，但腹泻病可能很严重并危及生命。如果受感染宿主得到充分补液，疾病通常在感染后2 - 5天内痊愈。在免疫功能低下的宿主中，病毒感染会持续存在，可在肠道外检测到病毒，并且病毒排泄可能会持续很长时间（数月）。轮状病毒感染几乎所有哺乳动物和一些鸟类，我们对轮状病毒发病机制的许多了解都来自动物模型研究，特别是小型动物模型（小鼠和兔子），但也包括大型动物（牛和仔猪）。由于从婴儿获取活检组织存在困难且缺乏临床需求，以及无法确定自然感染的确切时间，对儿童的研究受到限制。在所有能感染新生动物的物种中，疾病都与年龄有关；例如，在小鼠和兔子中，腹泻病是仅在出生后前两周发生感染的结果（Ciarlet等人，1998年；Starkey等人，1986年；Ramig，1988年；Ward等人，1990年；Burns等人，1995年），而动物成年后仍易受病毒感染。据报道，轮状病毒感染在人类从出生到老年都会反复发生，但2岁以后的大多数感染是无症状的，或与轻微的胃肠道症状有关。人类对轮状病毒引起的腹泻的年龄相关抵抗力被认为主要由获得性免疫介导，但无法直接测试人类是否也基于其他因素（如肠道发育和成熟）表现出对疾病的年龄依赖性抵抗力。目前，我们对轮状病毒发病机制的最佳理解依赖于在动物模型中获得的结果。
