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A peptide derived from the C‐terminus of PB 1 inhibits influenza virus replication by interfering with viral polymerase assembly
Author(s) -
Li Chunfeng,
Ba Qi,
Wu Aiping,
Zhang Hong,
Deng Tao,
Jiang Taijiao
Publication year - 2013
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12107
Subject(s) - polymerase , viral replication , rna polymerase , influenza a virus , rna dependent rna polymerase , virology , heterotrimeric g protein , biology , small interfering rna , virus , orthomyxoviridae , rna , microbiology and biotechnology , chemistry , biochemistry , gene , signal transduction , g protein
Efficient assembly of the influenza virus RNA ‐dependent RNA polymerase, a heterotrimeric complex formed by three subunits ( PA , PB 1 and PB 2) 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 731–757 of PB 1 ( PB 1 731–757 ) can disrupt the interaction between the C‐terminal part of PB 1 (denoted as PB 1c corresponding to PB 1 676–757 ) and the N‐terminal part of PB 2 (denoted as PB 2n corresponding to PB 2 1–40 ). We further show that PB 1 731–757 is capable of inhibiting viral polymerase activity and viral replication. Interestingly, we find that PB 1 731–757 interacts with PB 1c rather than PB 2n. Furthermore, mutational analyses show that the hydrophobic sites of PB 1c play an essential role in the PB 1c– PB 1 731–757 interaction. The characterization of the inhibitory effect of PB 1 731–757 on viral polymerase activity and viral replication could offer a potential target for anti‐influenza drug development. Structured digital abstractPB2n 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]