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Genetic characterization and molecular epidemiological analysis of novel enterovirus EV-B80 in China.

ABSTRACT: Enterovirus B80 (EV-B80) is a newly identified serotype belonging to the enterovirus B species. To date, only two full-length genomic sequences of EV-B80 are available in GenBank, and few studies on EV-B80 have been conducted in China or worldwide. More information and research on EV-B80 is needed to assess its genetic characteristics, phylogenetic relationships, and association with enteroviral diseases. In this study, we report the phylogenetic characteristics of three Xinjiang EV-B80 strains and one Tibet EV-B80 strain in China. The full-length genomic sequences of four strains show 78.8-79% nucleotide identity and 94-94.2% amino acid identity with the prototype of EV-B80, indicating a tendency for evolution. Based on a maximum likelihood phylogenetic tree based on the entire VP1 region, three genotypes (A-C) were defined, revealing the possible origin of EV-B80 strains in the mainland of China. Recombination analysis revealed intraspecies recombinations in all four EV-B80 strains in nonstructural regions along with two recombination patterns. Due to the geographic factor, the coevolution of EV-B strains formed two different patterns of circulation. An antibody seroprevalence study against EV-B80 in two Xinjiang prefectures also showed that EV-B80 strains were widely prevalent in Xinjiang, China, compared to other studies on EV-B106 and EV-B89. All four EV-B80 strains are not temperature sensitive, showing a higher transmissibility in the population. In summary, this study reports the full-length genomic sequences of EV-B80 and provides valuable information on global EV-B80 molecular epidemiology.

SUBMITTER: Han Z

PROVIDER: S-EPMC6258725 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Enterovirus 71 (EV-A71) is one of the predominant etiological agents of hand, foot and mouth disease (HMFD), which can cause severe central nervous system infections in young children. There is no clinically approved vaccine or antiviral agent against HFMD. The SP40 peptide, derived from the VP1 capsid of EV-A71, was reported to be a promising antiviral peptide that targeted the host receptor(s) involved in viral attachment or entry. So far, the mechanism of action of SP40 peptide is unknown. In this study, interactions between ten reported cell receptors of EV-A71 and the antiviral SP40 peptide were evaluated through molecular docking simulations, followed by in vitro receptor blocking with specific antibodies. The preferable binding region of each receptor to SP40 was predicted by global docking using HPEPDOCK and the cell receptor-SP40 peptide complexes were refined using FlexPepDock. Local molecular docking using GOLD (Genetic Optimization for Ligand Docking) showed that the SP40 peptide had the highest binding score to nucleolin followed by annexin A2, SCARB2 and human tryptophanyl-tRNA synthetase. The average GoldScore for 5 top-scoring models of human cyclophilin, fibronectin, human galectin, DC-SIGN and vimentin were almost similar. Analysis of the nucleolin-SP40 peptide complex showed that SP40 peptide binds to the RNA binding domains (RBDs) of nucleolin. Furthermore, receptor blocking by specific monoclonal antibody was performed for seven cell receptors of EV-A71 and the results showed that the blocking of nucleolin by anti-nucleolin alone conferred a 93% reduction in viral infectivity. Maximum viral inhibition (99.5%) occurred when SCARB2 was concurrently blocked with anti-SCARB2 and the SP40 peptide. This is the first report to reveal the mechanism of action of SP40 peptide in silico through molecular docking analysis. This study provides information on the possible binding site of SP40 peptide to EV-A71 cellular receptors. Such information could be useful to further validate the interaction of the SP40 peptide with nucleolin by site-directed mutagenesis of the nucleolin binding site.

Dataset Information

Genetic characterization and molecular epidemiological analysis of novel enterovirus EV-B80 in China.

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