Structure and Genotypes of Noroviruses
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ABSTRACT:
SUBMITTER: Chan M
PROVIDER: S-EPMC7173473 | biostudies-literature | 2017 Jan
REPOSITORIES: biostudies-literature
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Project description:Noroviruses constitute a major genus in the family Caliciviridae, which contains icosahedral viruses with positive-sense single-stranded RNA genome. In humans, these constantly evolving viruses are the cause of sporadic and epidemic gastroenteritis. Despite a lack of a reproducible cell culture system or a small animal model, remarkable progress has been made in our understanding of the molecular biology, immunology, structural biology, and evolution of human noroviruses. This understanding is further enhanced by studies of nonhuman noroviruses and animal caliciviruses that are cultivatable. The main focus of this chapter is to review our current understanding of the structural biology of noroviruses in particular and of caliciviruses in general, with an emphasis on the unique modular organization of the capsid that allows for strain-dependent variations in glycan recognition and antigenicity to facilitate sustained virus evolution. Finally, structures of the proteins are reviewed that are critical for virus replication and that can be targeted in the design of small molecule drugs for use as effective antivirals.
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Project description:To determine the genogroups and genotypes of bovine enteric caliciviruses (BECVs) circulating in calves, we determined the complete capsid gene sequences of 21 BECVs. The nucleotide and predicted amino acid sequences were compared phylogenetically with those of known human and animal enteric caliciviruses. Based on these analyses, 15 BECVs belonged to Norovirus genogroup III and genotype 2 (GIII/2) and were genetically distinct from human Norovirus GI and GII. Six BECVs had capsid gene sequences similar to that of the unclassified Nebraska (NB)-like BECV. The 15 bovine noroviruses (BoNVs) were more closely related to Bo/NLV/Newbury-2/76/UK (GIII/2) and other known genotype 2 BoNVs than to genotype 1 Bo/NLV/Jena/80/DE. The BoNV Bo/CV521-OH/02/US showed high nucleotide and amino acid identities (84 and 94%, respectively) with the capsid gene of Bo/NLV/Newbury-2/76/UK, whereas the nucleotide and amino acid sequences of the RNA polymerase gene were more closely related to those of Bo/NLV/Jena/80/DE (77 and 87% identities, respectively) than to those of Bo/NLV/Newbury-2/76/UK (69 and 69% identities, respectively), suggesting that Bo/CV521-OH/02/US is a genotype 1-2 recombinant. Gene conversion analysis by the recombinant identification program and SimPlot also predicted that Bo/CV521-OH/02/US was a recombinant. Six NB-like BECVs shared 88 to 92% nucleotide and 94 to 99.5% amino acid identities with the NB BECV in the capsid gene. The results of this study demonstrate genetic diversity in the capsid genes of BECVs circulating in Ohio veal calves, provide new data for coinfections with distinct BECV genotypes or genogroups, and describe the first natural BoNV genotype 1-2 recombinant, analogous to the previously reported human norovirus recombinants.
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Project description:Human noroviruses are major causative agents of sporadic and epidemic gastroenteritis both in children and adults. Currently there are no licensed therapeutic intervention measures either in terms of vaccines or drugs available for these highly contagious human pathogens. Genetic and antigenic diversity of these viruses, rapid emergence of new strains, and their ability to infect a broad population by using polymorphic histo-blood group antigens for cell attachment, pose significant challenges for the development of effective antiviral agents. Despite these impediments, there is progress in the design and development of therapeutic agents. These include capsid-based candidate vaccines, and potential antivirals either in the form of glycomimetics or designer antibodies that block HBGA binding, as well as those that target essential non-structural proteins such as the viral protease and RNA-dependent RNA polymerase. In addition to these classical approaches, recent studies suggest the possibility of interferons and targeting host cell factors as viable approaches to counter norovirus infection. This review provides a brief overview of this progress.
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