A Viral Enterotoxin
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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 ente-rocytes 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, partieularly in small animal models (miee and rabbits), but also in larger animals (eows and piglets). Studies in ehildren are limited due to the diffieulty and laek of elinieal need of obtaining biopsies from infants and the inability to determine the preeise time of natural infeetions. In all animaI speeies where naive animals ean be infeeted, disease is age-dependent; for example, in miee and rabbits, diarrheal disease is the outeome of infeetions that oeeur 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 suseeptible to viral infeetion into adulthood. Rotavirus infeetions have been reported to oeeur repeatedly in humans from birth to old age, but the majority of infeetions after the first 2 years of life are asymptomatie or assoeiated with mild gastrointestinal symptoms. The age-related resistanee to rotavirus-indueed diarrhea in humans is thought to be mediated primarily by aequired immunity, but it is not possible to direetly test if humans also exhibit an age-dependent resistanee to disease based on other faetors sueh as intestinal development and maturation. Currently, our best understanding of the meehanisms of rotavirus pathogenesis rely on results obtained in animal models.
KeywordsDiarrheal Disease Chloride Secretion NSP4 Protein Host Range Restriction Glycoprotein NS28
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