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RESEARCH PRODUCT

Molecular Virology of Enteric Viruses (with Emphasis on Caliciviruses)

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description

Human caliciviruses are members of the family Caliciviridae and are responsible for a majority of the outbreaks of acute nonbacterial gastroenteritis. In fact, they now are considered a common cause of sporadic cases of diarrhea in the community (Glass et al., 2000b; Koopmans et al., 2002; Lopman et al., 2002; Hutson et al., 2004). These viruses were implicated in as many as 95% of the reported viral gastroenteritis outbreaks examined over a 4.5-year period in the United States (Fankhauser et al., 2002), and similar high incidence rates have been found in other studies (Maguire et al., 1999; Glass et al., 2000b; Koopmans et al., 2000; Lopman et al., 2003). Common features of the Caliciviridae include the presence of a single major structural protein from which the capsid is constructed and 32 cup-shaped depressions on the surface of the virion arranged in an icosahedral symmetry. The name of the family was derived from the Latin word calix, which means cup or goblet, and refers to the surface hollows (Madeley, 1979). Another major feature of Caliciviridae is the absence of a methylated cap at the 5′ end of the viral RNA. Instead, a small protein (VPg) of ∼10 × 10 to 12 × 10 kDa is covalently linked to the viral RNA and is considered essential for the infectivity of the RNA (Black et al., 1978; Ando et al., 2000). Norwalk virus was the first human enteric calicivirus to be discovered, this after a gastrointestinal outbreak affecting both children and adults in an elementary school in Norwalk, Ohio (Kapikian et al., 1972). Over the next several years, other agents of epidemic viral gastroenteritis were described including Hawaii virus, Montgomery County agent, Snow Mountain virus, Southampton virus, Toronto virus, and so forth. An interim scheme to classify these viruses on a morphological and physicochemical basis was proposed by Caul and Appleton (1982). Some of these viruses were antigenically related to Norwalk virus by IEM (immune electron microscopy) and crosschallenge studies, whereas others, like the Sapporo virus (Chiba et al., 1979), were found to be antigenically distinct (Nakata et al., 1996). Human caliciviruses have been classified into two distinct genera namely, Norovirus (previously called “Norwalk-like viruses” (NLVs) or “small round structured viruses”) and Sapovirus (formerly “Sapporo-like viruses,” or SLVs) (Green et al., 2000b; Mayo, 2002). The noroviruses and sapoviruses form distinct phylogenetic clades within Caliciviridae (Berke et al., 1997), and certain features of their viral genome organization distinguish them from