ArticleThe Journal of biological chemistry2014
A novel functional site in the PB2 subunit of influenza A virus essential for acetyl-CoA interaction, RNA polymerase activity, and viral replication.
Article in The Journal of biological chemistry, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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Who cites it
11 citing papers in PubMed, 22 citations in OpenAlex.
- Pharmacophores of Influenza Virus PA Endonuclease Inhibitors.Advances in experimental medicine and biology · 2026Review
- Therapeutic effect of Yinhuapinggan granules mediated through the intestinal flora in mice infected with the H1N1 influenza virus.Frontiers in microbiology · 2024Article
- Molecular and functional characterization of an evolutionarily conserved CREB-binding protein in the Lymnaea CNS.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2022Article
- Interaction of NEP with G Protein Pathway Suppressor 2 Facilitates Influenza A Virus Replication by Weakening the Inhibition of GPS2 to RNA Synthesis and Ribonucleoprotein Assembly.Journal of virology · 2021Article
- Focusing on the Influenza Virus Polymerase Complex: Recent Progress in Drug Discovery and Assay Development.Current medicinal chemistry · 2019Review
- Influenza A virus nucleoprotein is acetylated by histone acetyltransferases PCAF and GCN5.The Journal of biological chemistry · 2018Article
- Influenza A Virus-Host Protein Interactions Control Viral Pathogenesis.International journal of molecular sciences · 2017Review
- Fragment-Based Identification of Influenza Endonuclease Inhibitors.Journal of medicinal chemistry · 2016Article
- Functional Genomics Reveals Linkers Critical for Influenza Virus Polymerase.Journal of virology · 2015Article
- C646, a Novel p300/CREB-Binding Protein-Specific Inhibitor of Histone Acetyltransferase, Attenuates Influenza A Virus Infection.Antimicrobial agents and chemotherapy · 2015Article
- Compounds with anti-influenza activity: present and future of strategies for the optimal treatment and management of influenza. Part I: Influenza life-cycle and currently available drugs.Journal of preventive medicine and hygiene · 2014Review
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The PA, PB1, and PB2 subunits, components of the RNA-dependent RNA polymerase of influenza A virus, are essential for viral transcription and replication. The PB2 subunit binds to the host RNA cap (7-methylguanosine triphosphate (m(7)GTP)) and supports the endonuclease activity of PA to "snatch" the cap from host pre-mRNAs. However, the structure of PB2 is not fully understood, and the functional sites remain unknown. In this study, we describe a novel Val/Arg/Gly (VRG) site in the PB2 cap-binding domain, which is involved in interaction with acetyl-CoA found in eukaryotic histone acetyltransferases (HATs). In vitro experiments revealed that the recombinant PB2 cap-binding domain that includes the VRG site interacts with acetyl-CoA; moreover, it was found that this interaction could be blocked by CoA and various HAT inhibitors. Interestingly, m(7)GTP also inhibited this interaction, suggesting that the same active pocket is capable of interacting with acetyl-CoA and m(7)GTP. To elucidate the importance of the VRG site on PB2 function and viral replication, we constructed a PB2 recombinant protein and recombinant viruses including several patterns of amino acid mutations in the VRG site. Substitutions of the valine and arginine residues or of all 3 residues of the VRG site to alanine significantly reduced the binding ability of PB2 to acetyl-CoA and its RNA polymerase activity. Recombinant viruses containing the same mutations could not be replicated in cultured cells. These results indicate that the PB2 VRG sequence is a functional site that is essential for acetyl-CoA interaction, RNA polymerase activity, and viral replication.
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