A mechanism for priming and realignment during influenza A virus replication

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14 Scopus citations

Abstract

The influenza A virus genome consists of eight segments of singlestranded RNA. These segments are replicated and transcribed by a viral RNA-dependent RNA polymerase (RdRp) that is made up of the influenza virus proteins PB1, PB2, and PA. To copy the viral RNA (vRNA) genome segments and the cRNA segments, the replicative intermediate of viral replication, the RdRp must use two promoters and two different de novo initiation mechanisms. On the vRNA promoter, the RdRp initiates on the 3' terminus, while on the cRNA promoter, the RdRp initiates internally and subsequently realigns the nascent vRNA product to ensure that the template is copied in full. In particular, the latter process, which is also used by other RNA viruses, is not understood. Here we provide mechanistic insight into priming and realignment during influenza virus replication and show that it is controlled by the priming loop and a helix-loop-helix motif of the PB1 subunit of the RdRp. Overall, these observations advance our understanding of how the influenza A virus initiates viral replication and amplifies the genome correctly.

Original languageEnglish (US)
Article numbere01773-17
JournalJournal of virology
Volume92
Issue number3
DOIs
StatePublished - Feb 1 2018
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Keywords

  • ApG
  • Influenza A virus
  • Priming loop
  • RNA-dependent RNA polymerase
  • Realignment
  • Viral replication

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