Article

Norovirus Gastroenteritis, Carbohydrate Receptors, and Animal Models

Division of Infectious Diseases, Cincinnati Children's Hospital Medical Center, University of Cincinnati College of Medicine, Cincinnati, Ohio, United States of America.
PLoS Pathogens (Impact Factor: 7.56). 08/2010; 6(8):e1000983. DOI: 10.1371/journal.ppat.1000983
Source: PubMed

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    • "The viral capsids are featured by an interior shell and many exterior protrusions that are made by the shell (S) and the protruding (P) domain of the capsid protein, respectively . While the interior shells serve as the basic scaffold of the icosahedral virions, the surface protruding P dimers are responsible for virus–host interactions1011121314, including viral attachment and penetration (reviewed in1516171819). As a result, the P domains can elicit neutralizing antibodies against infection of the three viruses202122, respectively, and therefore are attractive targets for subunit vaccine development against the three viruses[20,23]. "
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    ABSTRACT: Hepatitis E virus (HEV), norovirus (NoV), and astrovirus (AstV) are enterically-transmitted viral pathogens causing epidemic or endemic hepatitis (HEV) and gastroenteritis (NoV and AstV) respectively in humans, leading to significant morbidity and mortality worldwide. While a recombinant subunit vaccine against HEVs is available in China, there is no commercial vaccine or antiviral against NoV or AstV. We report here our development of a trivalent vaccine against the three viral pathogens through our new polymer vaccine technology. All HEV, NoV, and AstV are non-enveloped RNA viruses covered by a protein capsid, featuring surface protruding (P) proteins that are responsible for virus–host interaction. These dimeric P proteins elicit neutralizing antibody and are good targets for subunit vaccine development. The trivalent subunit vaccine was developed by fusion of the dimeric P domains of the three viruses together that formed tetramers. This trivalent vaccine elicited significantly higher antibody responses in mice against all three P domains than those induced by a mixture of the three free P domains (mixed vaccine). Furthermore, the post-immune antisera of the trivalent vaccine showed significantly higher neutralizing titers against HEV infection in cell culture and higher blocking activity against NoV binding to HBGA ligands than those of the post-immune sera of the mixed vaccine. Thus, the trivalent vaccine is a promising vaccine candidate against HEV, NoV, and AstV.
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    • ", 2013 ) . On the other hand , an individual ' s susceptibility to NoVs is correlated with his HBGA profile in vivo ( Tan and Jiang , 2010 ; Ruvoën - Clouet et al . , 2013 ) . "
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    ABSTRACT: This study aims to investigate if histo-blood group antigen (HBGA) expressing bacteria have any protective role on human norovirus (NoV) from acute heat stress. Eleven bacterial strains were included, belonging to Escherichia coli, Enterobacter cloacae, Enterobacter aerogenes, Clostridium difficile, Bifidobacterium adolescentis, and B. longum. HBGA expression of the bacteria as well as binding of human NoV virus-like particles (VLPs, GI.1, and GII.4 strains) to the bacteria were detected by flow cytometry. NoV VLPs pre-incubated with HBGA expressing or non-HBGA expressing bacteria were heated and detected by both direct ELISA and porcine gastric mucin-binding assay. The NoV-binding abilities of the bacteria correlated well with their HBGA expression profiles. Two HBGA expressing E. coli (LMG8223 and LFMFP861, both GI.1 and GII.4 binders) and one non-HBGA expressing E. coli (ATCC8739, neither GI.1 nor GII.4 binder) were selected for the heat treatment test with NoV VLPs. Compared with the same cell numbers of non-HBGA expressing E. coli, the presence of HBGA-expressing E. coli could always maintain higher antigen integrity, as well as mucin-binding ability of NoV VLPs of both GI.1 and GII.4 after heat-treatment at 90°C for 2 min. These results indicate that HBGA-expressing bacteria may protect NoVs during the food processing treatments, thereby facilitating their transmission.
    Full-text · Article · Jul 2015 · Frontiers in Microbiology
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    • "ORF2 is approximately 1.8 kb and encodes the 57 kDa major capsid protein, VP1, while ORF3 is approximately 0.6 kb and encodes a 33 kDa minor structural protein, VP2 (McFadden et al., 2011). VP1 is suggested to be involved in the recognition of the host cell receptor (Tan & Jiang, 2010) while VP2 is thought to be involved in the stability of the capsid but also seems to be vital for viral assembly (Glass et al., 2009). Recent studies have shown that murine norovirus has an additional ORF, ORF4, which overlaps ORF2 in an alternate reading frame (Thackray et al., 2007). "
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    ABSTRACT: Diarrhea is considered to be the second leading cause of death due to infections among children <5 years of age worldwide that may be caused by bacteria, parasites, viruses and non-infectious agents. The major causative agents of diarrhea in developing countries may vary from those in developed countries. Noroviruses are considered to be the most common cause of acute diarrhea in both children and adults in industrialized countries. On the other hand, there is lack of comprehensive epidemiological evidence from developing countries that norovirus is a major cause of diarrhea. In these regions, asymptomatic norovirus infections are very common, and similar detection rates have been observed in patients with diarrhea and asymptomatic persons. This review summarizes current knowledge of norovirus infection in developing countries and seeks to position infections with noroviruses among other enteropathogens as disease burden in these regions.
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