A mechanism for priming and realignment during influenza A virus replication

Judith Oymans, Aartjan J.W. te Velthuis*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

7 Citations (Scopus)

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
Article numbere01773-17
JournalJournal of Virology
Volume92
Issue number3
DOIs
Publication statusPublished - 1 Feb 2018

Fingerprint

RNA-directed RNA polymerase
RNA Replicase
Influenza A virus
Viral RNA
Virus Replication
virus replication
RNA
Complementary RNA
promoter regions
Orthomyxoviridae
genome
helix-loop-helix motifs
Helix-Loop-Helix Motifs
Genome
Viral Genome
RNA Viruses

Keywords

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

Cite this

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title = "A mechanism for priming and realignment during influenza A virus replication",
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.",
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author = "Judith Oymans and {te Velthuis}, {Aartjan J.W.}",
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A mechanism for priming and realignment during influenza A virus replication. / Oymans, Judith; te Velthuis, Aartjan J.W.

In: Journal of Virology, Vol. 92, No. 3, e01773-17, 01.02.2018.

Research output: Contribution to journalArticleAcademicpeer-review

TY - JOUR

T1 - A mechanism for priming and realignment during influenza A virus replication

AU - Oymans, Judith

AU - te Velthuis, Aartjan J.W.

PY - 2018/2/1

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N2 - 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.

AB - 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.

KW - ApG

KW - Influenza A virus

KW - Priming loop

KW - Realignment

KW - RNA-dependent RNA polymerase

KW - Viral replication

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DO - 10.1128/JVI.01773-17

M3 - Article

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