Dataset Information

MERS-related CoVs in hedgehogs from Hubei Province, China.

ABSTRACT: The emerging coronavirus diseases such as COVID-19, MERS, and SARS indicated that animal coronaviruses (CoVs) spillover to humans are a huge threat to public health. Therefore, we needed to understand the CoVs carried by various animals. Wild hedgehogs were collected from rural areas in Wuhan and Xianning cities in Hubei Province for analysis of CoVs. PCR results showed that 5 out of 51 (9.8%) hedgehogs (Erinaceus amurensis) were positive to CoVs in Hubei Province with 3 samples from Wuhan City and 2 samples from Xianning City. Phylogenetic analysis based on the partial sequence of RNA-dependent RNA polymerase showed that the CoVs from hedgehogs are classified into Merbecovirus of the genus Betacoronavirus; the hedgehog CoVs formed a phylogenetic sister cluster with human MERS-CoVs and bat MERS-related CoVs. Among the 12 most critical residues of receptor binding domain in MERS-CoV for binding human Dipeptidyl peptidase 4, 3 residuals were conserved between the hedgehog MERS-related CoV obtained in this study and the human MERS-CoV. We concluded that hedgehogs from Hubei Province carried MERS-related CoVs, indicating that hedgehogs might be important in the evolution and transmission of MERS-CoVs, and continuous surveillance of CoVs in hedgehogs was important.

SUBMITTER: Li D

PROVIDER: S-EPMC8464353 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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MERS-related CoVs in hedgehogs from Hubei Province, China.

Li Dan D Gong Xiao-Qing XQ Xiao Xiao X Han Hui-Ju HJ Yu Hao H Li Ze-Min ZM Yan Li-Na LN Gu Xiao-Lan XL Duan Shu-Hui SH Xue-jieYu

One health (Amsterdam, Netherlands) 20210923

The emerging coronavirus diseases such as COVID-19, MERS, and SARS indicated that animal coronaviruses (CoVs) spillover to humans are a huge threat to public health. Therefore, we needed to understand the CoVs carried by various animals. Wild hedgehogs were collected from rural areas in Wuhan and Xianning cities in Hubei Province for analysis of CoVs. PCR results showed that 5 out of 51 (9.8%) hedgehogs (<i>Erinaceus amurensis</i>) were positive to CoVs in Hubei Province with 3 samples from Wuha ...[more]

PMID: 34604493

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Project description:BackgroundThe disability weight (DW) reflects the severity of non-fatal outcomes and is an important parameter in calculating the burden of disease. However, the universality of the global, national, or subnational DWs remains controversial. This study aims to measure DWs specific to Hubei Province of China using non-parametric regression to anchor the DWs.MethodsPaired comparison (PC) data collected from a web-based survey in Hubei Province targeting the general population were used to estimate the DWs of 196 health states. Specifically, PC data from 33,925 respondents were analyzed by probit regression analysis, and the results were then anchored to 0-1 scale using non-parametric regression based on the DWs from Global Burden of Disease (GBD) 2013. The absolute DW values and rankings were compared to those in the Chinese disability weight measurement study, GBD 2013, and Japan.ResultsThe DWs for 196 health states ranged from 0.003 for mild distance vision impairment to 0.663 for severe heroin and opioid dependence in Hubei Province, China. Quite a lot mental disorders, such as moderate/severe episode of major depressive disorder, were considered more severe than the terminal phase with/without medication among Hubei residents. DW rankings of the health states are relatively stable in Hubei Province irrespective of the anchoring method used. A very small proportion (4 of 196, 2%) of DW rankings changed by 10 or more positions in China when compared with our results, but approximately 61% in GBD 2013 and 59% in Japan. Among the top 25 health states in this study, 9 of 11 health states categorized as mental, behavioral, and substance use disorders resulted in a lower ranking in GBD 2013, and all 6 states in Japan also showed a lower ranking, whereas China shared a similar ranking.ConclusionsThe burden of mental disorders among Hubei residents, especially moderate or severe major depressive disorder, deserves further attention. When using different anchoring methods, DW rankings were maintained relatively stable rather than the absolute values in Hubei. Substantial differences of DW rankings between our results and that in China, GBD 2013, and Japan draw attention to the need for deriving local disability for disease burden calculation.

Project description:Middle East respiratory syndrome coronavirus (MERS-CoV) binds to cellular receptor dipeptidyl peptidase 4 (DPP4) via the spike (S) protein receptor-binding domain (RBD). The RBD contains critical neutralizing epitopes and serves as an important vaccine target. Since RBD mutations occur in different MERS-CoV isolates and antibody escape mutants, cross-neutralization of divergent MERS-CoV strains by RBD-induced antibodies remains unknown. Here, we constructed four recombinant RBD (rRBD) proteins with single or multiple mutations detected in representative human MERS-CoV strains from the 2012, 2013, 2014, and 2015 outbreaks, respectively, and one rRBD protein with multiple changes derived from camel MERS-CoV strains. Like the RBD of prototype EMC2012 (EMC-RBD), all five RBDs maintained good antigenicity and functionality, the ability to bind RBD-specific neutralizing monoclonal antibodies (MAbs) and the DPP4 receptor, and high immunogenicity, able to elicit S-specific antibodies. They induced potent neutralizing antibodies cross-neutralizing 17 MERS pseudoviruses expressing S proteins of representative human and camel MERS-CoV strains identified during the 2012-2015 outbreaks, 5 MAb escape MERS-CoV mutants, and 2 live human MERS-CoV strains. We then constructed two RBDs mutated in multiple key residues in the receptor-binding motif (RBM) of RBD and demonstrated their strong cross-reactivity with anti-EMC-RBD antibodies. These RBD mutants with diminished DPP4 binding also led to virus attenuation, suggesting that immunoevasion after RBD immunization is accompanied by loss of viral fitness. Therefore, this study demonstrates that MERS-CoV RBD is an important vaccine target able to induce highly potent and broad-spectrum neutralizing antibodies against infection by divergent circulating human and camel MERS-CoV strains. MERS-CoV was first identified in June 2012 and has since spread in humans and camels. Mutations in its spike (S) protein receptor-binding domain (RBD), a key vaccine target, have been identified, raising concerns over the efficacy of RBD-based MERS vaccines against circulating human and camel MERS-CoV strains. Here, we constructed five vaccine candidates, designated 2012-RBD, 2013-RBD, 2014-RBD, 2015-RBD, and Camel-RBD, containing single or multiple mutations in the RBD of representative human and camel MERS-CoV strains during the 2012-2015 outbreaks. These RBD-based vaccine candidates maintained good functionality, antigenicity, and immunogenicity, and they induced strong cross-neutralizing antibodies against infection by divergent pseudotyped and live MERS-CoV strains, as well as antibody escape MERS-CoV mutants. This study provides impetus for further development of a safe, highly effective, and broad-spectrum RBD-based subunit vaccine to prevent MERS-CoV infection.

Dataset Information

MERS-related CoVs in hedgehogs from Hubei Province, China.

Publications

MERS-related CoVs in hedgehogs from Hubei Province, China.

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