ArticleGene2015
The hepatitis E virus ORF1 'X-domain' residues form a putative macrodomain protein/Appr-1″-pase catalytic-site, critical for viral RNA replication.
Article in Gene, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 papers.
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Who cites it
49 citing papers in PubMed.
- Macrodomain ADP-ribose binding but not ADP-ribosylhydrolase activity is critical for chikungunya virus infection ofbioRxiv : the preprint server for biology · 2025Article
- Identification of key candidates associated with chronic hepatitis E viral infection.Bioinformation · 2025Article
- Role of microRNAs in chronic hepatitis E viral infection.Bioinformation · 2025Article
- Mutation of a highly conserved isoleucine residue in loop 2 of several β-coronavirus macrodomains indicates that enhanced ADP-ribose binding is detrimental for replication.Journal of virology · 2024Article
- Mutation of a highly conserved isoleucine residue in loop 2 of severalbioRxiv : the preprint server for biology · 2024Article
- The hepatitis E virus ORF1 hypervariable region confers partial cyclophilin dependency.The Journal of general virology · 2023Article
- An Update on the Current State of SARS-CoV-2 Mac1 Inhibitors.Pathogens (Basel, Switzerland) · 2023Review
- PARP12 is required to repress the replication of a Mac1 mutant coronavirus in a cell- and tissue-specific manner.Journal of virology · 2023Article
- A single inactivating amino acid change in the SARS-CoV-2 NSP3 Mac1 domain attenuates viral replication in vivo.PLoS pathogens · 2023Article
- Thrombin cleavage of the hepatitis E virus polyprotein at multiple conserved locations is required for genome replication.PLoS pathogens · 2023Article
- PARP12 is required to repress the replication of a Mac1 mutant coronavirus in a cell and tissue specific manner.bioRxiv : the preprint server for biology · 2023Article
- Characterization of anPathogens (Basel, Switzerland) · 2023Article
- A single inactivating amino acid change in the SARS-CoV-2 NSP3 Mac1 domain attenuates viral replication and pathogenesisbioRxiv : the preprint server for biology · 2023Article
- Article
- Mono-ADP-ribosylation by PARP10 inhibits Chikungunya virus nsP2 proteolytic activity and viral replication.Cellular and molecular life sciences : CMLS · 2023Article
- Characteristics and Functions of HEV Proteins.Advances in experimental medicine and biology · 2023Article
- Structural aspects of hepatitis E virus.Archives of virology · 2022Review
- Design, synthesis and evaluation of inhibitors of the SARS-CoV-2 nsp3 macrodomain.Bioorganic & medicinal chemistry · 2022Article
- Discovery of compounds that inhibit SARS-CoV-2 Mac1-ADP-ribose binding by high-throughput screening.Antiviral research · 2022Article
- Hepatitis E genotype 3 genome: A comprehensive analysis of entropy, motif conservation, relevant mutations, and clade-associated polymorphisms.Frontiers in microbiology · 2022Article
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Abstract
The hepatitis E virus (HEV) ORF1 gene encodes the non-structural polyprotein wherein the 'X-domain' still remains poorly defined. Cellular X-domain associated macrodomain protein/ADP-ribose-1″-monophosphatase (Appr-1″-pase) activities are also reported in coronaviruses (CoV), including identification of its homologs in alpha and rubella viruses. The present study investigated the role(s) of X-domain residues in HEV replication cycle. In silico analysis showed a high degree of evolutionary conservation of X-domain (a.a. 785-942) a.a. positions wherein the N-terminus residues 'Asn806, Asn809, His812, Gly815, Gly816, and Gly817' formed a potential catalytic-site homolog of CoVAppr-1″-pase. To experimentally test this prediction, X-domain 'active-site' residues were subjected to mutational analysis using the HEV-SAR55 replicon (pSK-GFP). FACS analysis of mutant RNA transfected S10-3 cells showed that Gly816Ala and Gly817Ala constructs completely abrogated HEV replication, similar to their Gly816Val and Gly817Val counterparts. However, 'Gly815Ala' mutant replicated very poorly in contrast to 'Gly815Val' that completely abolished GFP synthesis. Furthermore, while 'Asn806Ala' mutant retained RNA replication, the 'Asn809Ala' and His812Leu mutants showed non-viability. Notably, in a sequential-nucleotide mutation analysis, the dispensability of X-domain in HEV replication at transcriptional level has already been demonstrated (Parvez, 2013b). Taken together, the present data strongly argue for an essential role of X-domain residues (Asn809, His812, Gly816 and Gly817) at post-translational level, indicating its involvement in viral replication. In conclusion, the speculated regulatory role of ORF1 X-domain in HEV replication cycle critically depends on the 'Asn, Asn, His, Gly, Gly, Gly' segment/secondary structure. Nevertheless, further biochemical or biophysical characterizations of HEV X-domain associated Appr-1″-pase activity would only confirm its biological significance in virus or host-pathogenesis.
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