期刊
FEBS JOURNAL
卷 280, 期 4, 页码 1139-1149出版社
WILEY-BLACKWELL
DOI: 10.1111/febs.12107
关键词
influenza polymerase assembly; influenza virus; peptide inhibitor; subunit interaction; virus replication
资金
- National Foundation of Talent Youth [31125016]
- Project '973' [2009CB918503, 2010CB534003]
- National Key Laboratory Open Foundation [2010KF04]
- Chinese Science and Technology Major Project [2008ZX10004-016, 2013ZX10004061-002]
- National Natural Science Foundation of China [31070152]
- Institute of Pathogen Biology, Chinese Academy of Medical Sciences [2009IPB201]
Efficient assembly of the influenza virus RNA-dependent RNA polymerase, a heterotrimeric complex formed by three subunits (PA, PB1 and PB2) is critical for virus replication and pathogenicity. Therefore, interfering with the assembly of the RNA-dependent RNA polymerase complex could offer novel and effective anti-influenza therapeutics. In the present study, we show that a short peptide derived from amino acids 731757 of PB1 (PB1731757) can disrupt the interaction between the C-terminal part of PB1 (denoted as PB1c corresponding to PB1676757) and the N-terminal part of PB2 (denoted as PB2n corresponding to PB2140). We further show that PB1731757 is capable of inhibiting viral polymerase activity and viral replication. Interestingly, we find that PB1731757 interacts with PB1c rather than PB2n. Furthermore, mutational analyses show that the hydrophobic sites of PB1c play an essential role in the PB1cPB1731757 interaction. The characterization of the inhibitory effect of PB1731757 on viral polymerase activity and viral replication could offer a potential target for anti-influenza drug development. Structured digital abstract PB2n physically interacts with PB1c by pull down (View interaction) PB2n and PB1c physically interact by bimolecular fluorescence complementation (View interaction) PB1 (731-757) physically interacts with PB1c by pull down (View interaction) PB1 (731-757) and PB1c physically interact by bimolecular fluorescence complementation (View Interaction: 1, 2, 3, 4, 5) [Structured digital abstract was added on 11 February 2013 after original online publication]
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