Article: Crucial mutation in the exoribonuclease domain of nsp14 of PEDV leads to high genetic instability during viral replication.
2021 Volume 11, Issue 1, Page(s) 106
Abstract: Background: Coronavirus (CoV) nonstructural protein 14 (nsp14) has exoribonuclease (ExoN) activity, responsible for proofreading and contributing to replication fidelity. It has been reported that CoVs exhibit variable sensitivity to nsp14-ExoN ... ...
Abstract | Background: Coronavirus (CoV) nonstructural protein 14 (nsp14) has exoribonuclease (ExoN) activity, responsible for proofreading and contributing to replication fidelity. It has been reported that CoVs exhibit variable sensitivity to nsp14-ExoN deficiency. Betacoronavirus murine hepatitis virus (MHV) and severe acute respiratory syndrome (SARS)-CoV were viable upon nsp14-ExoN deficiency. While betacoronavirus Middle East respiratory syndrome (MERS)-CoV and SARS-CoV-2 were non-viable with disabled nsp14-ExoN. In this study, we investigated the nsp14-ExoN deficiency of alphacoronavirus porcine epidemic diarrhea virus (PEDV) in viral pathogenesis using reverse genetics. Results: Eight nsp14-ExoN deficient mutants, targeting the predicted active sites and the Zinc finger or mental-coordinating sites, of PEDV were designed. Only one mutant E191A with a mutation in the Mg Conclusion: The recombinant PEDV variants carrying mutations at the essential functional sites within nsp14-ExoN were either lethal or genetically unstable. Our finding further confirmed the critical role of nsp14-ExoN in CoV life cycle, suggesting that it may be a target for the design of universal anti-CoV drugs. |
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Language | English |
Publishing date | 2021-06-07 |
Publishing country | England |
Document type | Journal Article |
ZDB-ID | 2593367-X |
ISSN | 2045-3701 |
ISSN | 2045-3701 |
DOI | 10.1186/s13578-021-00598-1 |
Database | MEDical Literature Analysis and Retrieval System OnLINE |
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