Functional association between viral and cellular transcription during influenza virus infection

Rev Med Virol. 2006 Sep-Oct;16(5):329-45. doi: 10.1002/rmv.512.

Abstract

Influenza viruses replicate and transcribe their segmented negative-sense single-stranded RNA genome in the nucleus of the infected host cell. All RNA synthesising activities associated with influenza virus are performed by the virally encoded RNA-dependent RNA polymerase (RdRp) that consists of three subunits, PA, PB1 and PB2. However, viral transcription is critically dependent on on-going cellular transcription, in particular, on activities associated with the cellular DNA-dependent RNA polymerase II (Pol II). Thus, the viral RdRp uses short 5' capped RNA fragments, derived from cellular Pol II transcripts, as primers for viral mRNA synthesis. These capped RNA primers are generated by cleavage of host Pol II transcripts by an endonuclease activity associated with the viral RdRp. Moreover, some viral transcripts require splicing and since influenza virus does not encode splicing machinery, it is dependent on host splicing, an activity also related to Pol II transcription. Despite these functional links between viral and host Pol II transcription, there has been no evidence that a physical association existed between the two transcriptional machineries. However, recently it was reported that there is a physical interaction between the trimeric viral RdRp and cellular Pol II. The viral RdRp was found to interact with the C-terminal domain (CTD) of initiating Pol II, at a stage in the transcription cycle when capping takes place. It was therefore proposed that this interaction may be required for the viral RNA (vRNA) polymerase to gain access to capped RNA substrates for endonucleolytic cleavage. The virus not only relies on cellular factors to support its own RNA synthesis, but also subverts cellular pathways in order to generate an environment optimised for viral multiplication. In this respect, the interaction of the viral NS1 protein with factors involved in cellular pre-mRNA processing is of particular relevance. The virus also alters the distribution of Pol II on cellular genes, leading to a reduction in elongating Pol II thereby contributing to the phenomenon known as host shut-off.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cell Nucleus / enzymology
  • Cell Nucleus / virology
  • Humans
  • Orthomyxoviridae / genetics*
  • Orthomyxoviridae Infections / enzymology
  • Orthomyxoviridae Infections / genetics*
  • Orthomyxoviridae Infections / virology*
  • RNA Polymerase II / physiology*
  • Transcription, Genetic*
  • Viral Proteins / genetics
  • Viral Proteins / metabolism
  • Virus Replication*

Substances

  • Viral Proteins
  • RNA Polymerase II