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Identification of A Novel Viral Protein Expressed from the PB2 Segment of Influenza A Virus

tetano

Editor, Senior Moderator
J Virol. 2015 Oct 21. pii: JVI.02175-15. [Epub ahead of print]
[h=1]Identification of A Novel Viral Protein Expressed from the PB2 Segment of Influenza A Virus.[/h] Yamayoshi S[SUP]1[/SUP], Watanabe M[SUP]2[/SUP], Goto H[SUP]2[/SUP], Kawaoka Y[SUP]3[/SUP].
[h=3]Author information[/h]

[h=3]Abstract[/h] Over the past two decades, several novel influenza viral proteins have been identified that modulate viral infections in vitro and/or in vivo. The PB2 segment, which is one of the longest influenza A virus segments, is known to encode only one viral protein, PB2. Here, we used RT-PCR targeting viral mRNAs transcribed from the PB2 segment to look for novel viral proteins encoded by spliced mRNAs. We identified a new viral protein, termed PB2-S1, encoded by a novel spliced mRNA in which the region corresponding to nucleotides 1513-1894 of the PB2 mRNA was deleted. PB2-S1 was detected in virus-infected cells and in cells transfected with a protein expression plasmid encoding PB2. PB2-S1 localized to mitochondria, inhibited the RIG-I-dependent interferon signaling pathway, and interfered with viral polymerase activity depending on its PB1 binding capability. The nucleotide sequences around the splicing donor and acceptor sites for PB2-S1 were highly conserved among human pre-2009 H1N1 viruses but not among human H1N1pdm and H3N2 viruses. PB2-S1-deficient viruses, however, showed similar growth kinetics in MDCK cells and virulence in mice to those of wild-type virus. The biological significance of PB2-S1 to the replication and pathogenicity of seasonal H1N1 influenza A viruses warrants further investigation.
[h=4]IMPORTANCE:[/h] Transcriptome analysis of cells infected with influenza A virus has improved our understanding of the host response to viral infection because such analysis yields considerable information about both in vitro and in vivo viral infection. However, little attention has been paid to transcriptomes derived from the viral genome. Here, we focused on the splicing of mRNA expressed from the PB2 segment and identified a spliced viral mRNA encoding a novel viral protein. This result suggests that other as-yet unidentified viral proteins encoded in spliced mRNAs could be expressed in virus-infected cells. A viral transcriptome, including a viral spliceosome, should be evaluated to gain new insights into influenza virus infection.
Copyright ? 2015, American Society for Microbiology. All Rights Reserved.


PMID: 26491155 [PubMed - as supplied by publisher]
 
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