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  • CLINICAL MICROBIOLOGY REVIEWS, Jan. 1989, p. 51-89 Vol. 2, No. 1 0893-8512/89/010051-39$02.00/0 Copyright A) 1989, American Society for Microbiology

    Human Viral Gastroenteritis MARY L. CHRISTENSEN

    Department of Pathology, Northwestern University Medical School, Chicago, Illinois 60611, and Virology Laboratory, Department ofPathology, The Children's Memorial Hospital, Chicago, Illinois 60614*

    INTRODUCTION................................... 51 ROTAVIRUSES................................... 52

    Introduction ................................... 52 Molecular Biology and Classification................................... 52 Epidemiology................................... 53 Clinical Features and Pathogenesis ................................... 56

    Clinical features ................................... 56 Pathogenesis................................... 56

    Laboratory Methods and Diagnosis ................................... 57 Cultivation ................................... 57 EM................................... 58 EIAs and LA tests ................................... 58 Other detection methods ................................... 61 Antibody detection................................... 61

    Immunology ................................... 61 Prevention................................... 65

    Vaccines ................................... 65 Chemical disinfection................................... 66

    Treatment................................... 67 ADENOVIRUSES................................... 68

    Introduction ................................... 68 Molecular Biology and Classification................................... 68 Epidemiology................................... 68 Clinical Features ................................... 70 Laboratory Diagnosis ................................... 71 Immunology ................................... 71 Prevention and Treatment ................................... 72

    NORWALK AND NORWALK-LIKE VIRUSES ................................... 72 Introduction ................................... 72 Physical Characteristics ................................... 72 Epidemiology................................... 72 Clinical Features and Pathogenesis ................................... 73

    Clinical features...............................................................................................................73 Pathogenesis................................... 73

    Laboratory Diagnosis ................................... 74 Cell and organ culture................................... 74 In vitro assays................................... 74

    Immunology ................................... 75 Prevention and treatment................................... 75

    CALICIVIRUSES................................... 76 ASTROVIRUSES ................................... 77 CORONAVIRUSES ................................... 77 ACKNOWLEDGMENTS ................................... 78 LITERATURE CITED ................................... 78

    INTRODUCTION and Norwalk-like viruses (6, 87, 187, 278, 401), caliciviruses (112, 231), astroviruses, (229, 230), and possibly coronavi-

    Until 15 years ago, the causes of acute nonbacterial ruses (322). The common enteroviruses are associated with gastroenteritis were unknown. However, during the 1970s, a relatively few cases of viral gastroenteritis (15). The various number of viruses associated with this clinical syndrome viral agents were discovered by the method of electron were discovered, and their presence in the stools of patients microscopy (EM), using EM to examine stools or intestinal with gastroenteritis were eventually correlated with the biopsies from these patients (18, 33, 110, 253). As a group, disease process. These various viruses include rotaviruses these viruses are fastidious and cannot be cultivated in (18, 109), fastidious fecal adenoviruses (77, 110), Norwalk routine cell culture (22, 53, 70, 77, 84, 110). Some can now be

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  • 52 CHRISTENSEN

    propagated by using special cell types or techniques or both (320, 353, 372). In addition, a variety of in vitro detection systems, including enzyme immunoassays (149, 175, 333, 408), radioimmunoassays (137, 141, 181, 264), latex aggluti- nation (140, 169), and nucleic acid hybridization techniques (116, 175), have been developed for their rapid detection. The detection and identification of these agents are impor-

    tant since viral gastroenteritis is the second most common clinical entity in developed countries, second only to viral upper respiratory tract illness (188). Worldwide, acute gas- troenteritis and its associated dehydration afflicts almost 500 million children annually. In underdeveloped or developing countries, acute gastroenteritis, including viral gastroente- ritis, is the leading cause of death of children under the age of 4 years (360).

    Since 1980, a wealth of literature has developed covering many aspects of these viruses and the infections they cause, including their molecular biology, epidemiology, immunol- ogy, and clinical features. In addition, detection tests for routine use have been developed for rotaviruses (310) and fecal adenoviruses (333) and experimental rotavirus vaccines have been developed (184, 377, 379, 380). Of these viruses, rotaviruses are the most common known cause of viral gastroenteritis in infants and young children, with the fastid- ious fecal adenoviruses most likely being the second most common cause in this age group (301, 369). Calici-, astro-, and coronaviruses are probably responsible for a minority of illness in the young age group (253, 302). In contrast, the Norwalk and Norwalk-like viruses have caused considerable numbers of outbreaks of gastroenteritis among older chil- dren, adolescents, and adults (136, 137, 189).

    ROTAVIRUSES

    Introduction

    Rotaviruses are in the Reoviridae family, the members of which possess a double-layer of icosahedral shells of approx- imately 70 nm in diameter, with a core of double-stranded ribonucleic acid (dsRNA). Rotaviruses infect a wide variety of mammals and birds as well as humans. Most rotaviruses from various species are similar and share a common group antigen, which is associated with the inner capsid layer. However, some rotaviruses do not possess this group anti- gen. Rotaviruses are responsible for a significant proportion of gastroenteritis in small children and infants, as well as for causing gastroenteritis in the elderly. Similarly, animal and avian rotaviruses are responsible for gastroenteritis in the young of their corresponding species.

    Molecular Biology and Classification Rotaviruses contain a dsRNA genome consisting of 11

    segments, ranging in molecular weight from 0.4 x 106 to 2.0 x 106 (275). These 11 segments can be separated by poly- acrylamide gel electrophoresis (PAGE) (103, 182), using the method of Laemmli (212). Different rotavirus isolates fre- quently exhibit differences in the electrophoretic mobilities of their 11 segments. Rotaviruses exhibiting these different electrophoretic mobilities have been termed electrophe- rotypes. Although frequently many of the rotaviruses iso- lated in the same geographical location at the same time of year may exhibit similar or identical electrophoretic mobili- ties, there has been considerable variation in electrophoretic mobilities of viruses isolated during different seasons or at different locales during the same season. For example,

    Rodger et al. (304) described 19 different electropherotypes isolated in Melbourne, Australia, from 1973 to 1979; Albert et al. (3) described 9 different electropherotypes isolated in Indonesia in 1978 and 1979; Rodriquez et al. (306) reported on 10 different electropherotypes seen in two nosocomial outbreaks for a 6-month period in 1979 and 1980 in Wash- ington, D.C.; and Spencer et al. (340) described 32 different electropherotypes seen in Santiago, Chile, from 1979 to 1981. Attempts have been made to characterize and classify human rotaviruses based on their electrophoretic mobilities. However, the variation has been too great, except for two patterns of electrophoretic mobility that have been distin- guished (103, 182). These are the "short" pattern and the "long" pattern, in which gene segments 10 and 11 migrate more slowly, creating a short pattern, or more rapidly, creating a long pattern, in the polyacrylamide gels (103, 182). To study the problem of genetic relatedness among various electropherotypes, Flores et al. (115) prepared single- stranded RNA probes for hybridization to gene segments which consist of dsRNA. They found that corresponding gene segments that exhibited similar migration patterns did not necessarily exhibit RNA homology when studied by hybridization with the probes. Conversely, some corre- sponding gene segments that exhibited RNA homology with the probes did not have the same electrophoretic migration pattern. Thus, they concluded that similarities or differences in electrophoretic mobility did not always reflect similarities or differences in genetic relatedness between various RNA segments (115). However, it has been shown that electro- pherotypes are excellent markers for identifying and follow- ing the spread of viruses from one individual to another in discrete outbreaks; thus, they are good for providing epide- miological information (47, 304).

    In addition to segments 10 and 11, three gene segments are of particular interest since they code for three major rota- viral antigens, VP4, VP6, and VP7. The major antigens of rotavirus and the genes that code for them are shown in Table 1. Gene segment 4 codes for VP4 (179, 219, 222, 243, 335). Origina

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