Caliciviruses
المؤلف:
Stefan Riedel, Jeffery A. Hobden, Steve Miller, Stephen A. Morse, Timothy A. Mietzner, Barbara Detrick, Thomas G. Mitchell, Judy A. Sakanari, Peter Hotez, Rojelio Mejia
المصدر:
Jawetz, Melnick, & Adelberg’s Medical Microbiology
الجزء والصفحة:
28e , p552-554
2025-12-13
38
In addition to rotaviruses and noncultivable adenoviruses, members of the family Caliciviridae are important agents of viral gastroenteritis in humans. The most significant members are the noroviruses, the prototype strain being Norwalk virus. Properties of caliciviruses are summarized in Table 1.
Table1. Important Properties of Caliciviruses
Classification and Antigenic Properties
Caliciviruses are similar to picornaviruses but are slightly larger (27–40 nm) and contain a single major structural protein (Figure 1). They exhibit a distinctive morphology in the electron microscope (Figure 2). The family Caliciviridae is divided into five genera: Norovirus, which includes the Norwalk viruses; Sapovirus, which includes the Sapporo-like viruses; Nebovirus, which includes bovine enteric viruses; Lagovirus, the rabbit hemorrhagic disease virus; and Vesivirus, which includes vesicular exanthem virus of swine, feline calicivirus, and marine viruses found in pinnipeds, whales, and fish. The first two genera contain human viruses that cannot be cultured; the latter two genera contain animal strains that can be grown in vitro. Rabbit hemorrhagic disease virus was introduced in 1995 in Australia as a biologic control agent to reduce that country’s population of wild rabbits.
Fig1. X-ray structure of the Norwalk virus capsid (left). The capsid subunit structure is illustrated (right panel). S, P1, and P2 domains are shaded in blue, red, and yellow, respectively. (Courtesy of BVV Prasad.)
Fig2. Electron micrographs of virus particles found in stools of patients with gastroenteritis. These viruses were visualized after negative staining. Specific viruses and the original magnifications of the micrographs are as follows. A: Rotavirus (185,000×). B: Enteric adenovirus (234,000×). C: Coronavirus (249,000×). D: Torovirus (coronavirus) (249,000×). E: Calicivirus (250,000×). F: Astrovirus (196,000×). G: Norwalk virus (calicivirus) (249,000×). H: Parvovirus (249,000×). The electron micrographs in panels C–H were originally provided by T Flewett; panel E was originally obtained from CR Madeley. Bars, 100 nm. (Reproduced with permission from Graham DY, Estes MK: Viral infections of the intestine. In Gitnick G, et al [editors]. Principles and Practice of Gastroenterology and Hepatology. Elsevier 1988;566.)
Human calicivirus serotypes are not defined. Multiple genotypes of noroviruses have been detected. Three genogroups are associated with human gastroenteritis, designated GI, GII, and GIV. Since 2001, genotype GII.4 viruses have caused most viral gastroenteritis outbreaks worldwide. Noro viruses appear to undergo antigenic drift over time, probably in response to population immunity.
Cellular receptors for noroviruses are histocompatibility blood group antigens that are expressed on the mucosal epithelia of the digestive tract. A person’s secretor status is controlled by the fucosyltransferase 2 gene; secretor-negative individuals are resistant to infection with common strains of Norwalk virus.
Clinical Findings and Laboratory Diagnosis
Noroviruses (Norwalk virus) are the most important cause of epidemic viral gastroenteritis in adults (Table 2). Epidemic nonbacterial gastroenteritis is characterized by (1) absence of bacterial pathogens, (2) gastroenteritis with rapid onset and recovery and relatively mild systemic signs, and (3) an epidemiologic pattern of a highly communicable disease that spreads rapidly with no particular predilection in terms of age or geography. Various descriptive terms have been used in reports of different outbreaks (eg, epidemic viral gastroenteritis, viral diarrhea, and winter vomiting disease) depending on the predominant clinical feature.
Table2. Viruses Associated with Acute Gastroenteritis in Humans a
Norwalk viral gastroenteritis has an incubation period of 24–48 hours. The onset is rapid, and the clinical course is brief, lasting 12–60 hours; symptoms include diarrhea, nausea, vomiting, low-grade fever, abdominal cramps, head ache, and malaise. The illness can be incapacitating during the symptomatic phase, but hospitalization is rarely required. Norovirus infections are more likely to induce vomiting than those with Sapporo-like viruses. Dehydration is the most common complication in young and elderly individuals. Viral shedding may persist for as long as 1 month. No sequelae have been reported.
Volunteer experiments have shown that the appearance of Norwalk virus coincides with clinical illness. Anti body develops during the illness and is usually protective on a short-term basis against reinfection with the same agent. Long-term immunity does not correspond well to the presence of serum antibodies. Some volunteers can be reinfected with the same virus after about 2 years.
Reverse transcriptase PCR is the most widely used technique for detection of human caliciviruses in clinical specimens (feces, vomitus) and environmental samples (contaminated food, water). Because of the genetic diversity among circulating strains, the choice of PCR primer pairs is very important. There can be up to 100 billion viral genome copies per gram of feces at peak shedding (2–5 days after infection).
Electron microscopy can be used to detect virus particles in stool samples. However, norovirus particles are usually present in low concentration (unless the sample was collected at peak viral shedding) and are difficult to recognize; they can be identified by IEM. ELISA immunoassays based on recombinant virus-like particles can detect antibody responses, with a fourfold or greater rise in IgG antibody titer in acute and convalescent-phase sera indicative of a recent infection. However, the necessary reagents are not widely available, and the antigens are not able to detect responses to all antigenic types of noroviruses.
Epidemiology and Immunity
Human caliciviruses have worldwide distribution. Noroviruses are the most common cause of nonbacterial gastroenteritis in the United States, causing an estimated 21 million cases annually.
The viruses are most often associated with epidemic outbreaks of waterborne, foodborne, and shellfish-associated gastroenteritis. All age groups can be affected. Outbreaks occur throughout the year, with a seasonal peak during cooler months. Fecal–oral spread is the primary means of transmission. Most outbreaks involve foodborne or person-to-person transmission via fomites or aerosolization of contaminated body fluids (vomitus, fecal material). Outbreaks in closed settings, such as cruise ships and nursing homes, are typical.
Characteristics of norovirus include a low infectious dose (as few as 10 virus particles), relative stability in the environment, and multiple modes of transmission. It sur vives 10 ppm chlorine and heating to 60°C; it can maintain viability in steamed oysters.
No in vitro neutralization assay is available to study immunity. Volunteer challenge studies have shown that about 50% of adults are susceptible to illness. Norwalk virus anti body is acquired later in life than rotavirus antibody, which develops early in childhood. In developing countries, most children have developed norovirus antibodies by 4 years of age.
Treatment and Control
Treatment is symptomatic. The low infectious dose permits efficient transmission of the virus. Effective handwashing is probably the most important method to prevent norovirus infection and transmission. Because of the infectious nature of the stools, care should be taken in their disposal. Containment and disinfection of soiled areas and bedding can help decrease viral spread. Careful processing of food and education of food handlers are important because many foodborne outbreaks occur. Purification of drinking water and swim ming pool water should decrease norovirus outbreaks. There is no vaccine.
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