Crystal structure of a tick-borne flavivirus RNA-dependent RNA polymerase suggests a host adaptation hotspot in RNA viruses
| Autor: | Xiao-Dan Li, Peng Gong, Xuping Jing, Chen Yao, Hanzhong Wang, Bo Zhang, Zhenhua Zheng, Wenfu Yi, Jieyu Yang |
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| Rok vydání: | 2020 |
| Předmět: |
Models
Molecular AcademicSubjects/SCI00010 viruses RNA-dependent RNA polymerase Viral Nonstructural Proteins Crystallography X-Ray Host Adaptation Cell Line Encephalitis Viruses Tick-Borne 03 medical and health sciences Viral life cycle Transcription (biology) Cricetinae Genetics Animals Replicon Polymerase 030304 developmental biology 0303 health sciences biology Nucleic Acid Enzymes 030302 biochemistry & molecular biology RNA Methyltransferases biology.organism_classification RNA-Dependent RNA Polymerase Flavivirus biology.protein Viral genome replication |
| Zdroj: | Nucleic Acids Research |
| ISSN: | 1362-4962 |
| Popis: | The RNA-dependent RNA polymerases (RdRPs) encoded by RNA viruses represent a unique class of nucleic acid polymerases. RdRPs are essential in virus life cycle due to their central role in viral genome replication/transcription processes. However, their contribution in host adaption has not been well documented. By solving the RdRP crystal structure of the tick-borne encephalitis virus (TBEV), a tick-borne flavivirus, and comparing the structural and sequence features with mosquito-borne flavivirus RdRPs, we found that a region between RdRP catalytic motifs B and C, namely region B-C, clearly bears host-related diversity. Inter-virus substitutions of region B-C sequence were designed in both TBEV and mosquito-borne Japanese encephalitis virus backbones. While region B-C substitutions only had little or moderate effect on RdRP catalytic activities, virus proliferation was not supported by these substitutions in both virus systems. Importantly, a TBEV replicon-derived viral RNA replication was significantly reduced but not abolished by the substitution, suggesting the involvement of region B-C in viral and/or host processes beyond RdRP catalysis. A systematic structural analysis of region B-C in viral RdRPs further emphasizes its high level of structure and length diversity, providing a basis to further refine its relevance in RNA virus-host interactions in a general context. |
| Databáze: | OpenAIRE |
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