Preferential use of RNA leader sequences during influenza A transcription initiation in vivo

C. Geerts-Dimitriadou, R.W. Goldbach, R.J.M. Kormelink

Research output: Contribution to journalArticleAcademicpeer-review

21 Citations (Scopus)

Abstract

In vitro transcription initiation studies revealed a preference of influenza A virus for capped RNA leader sequences with base complementarity to the viral RNA template. Here, these results were verified during an influenza infection in MDCK cells. Alfalfa mosaic virus RNA3 leader sequences mutated in their base complementarity to the viral template, or the nucleotides 5' of potential base-pairing residues, were tested for their use either singly or in competition. These analyses revealed that influenza transcriptase is able to use leaders from an exogenous mRNA source with a preference for leaders harboring base complementarity to the 3'-ultimate residues of the viral template, as previously observed during in vitro studies. Internal priming at the 3'-penultimate residue, as well as “prime-and-realign” was observed. The finding that multiple base-pairing promotes cap donor selection in vivo, and the earlier observed competitiveness of such molecules in vitro, offers new possibilities for antiviral drug design.
Original languageEnglish
Pages (from-to)27-32
JournalVirology
Volume409
Issue number1
DOIs
Publication statusPublished - 2011

Keywords

  • b-virus genome
  • complete nucleotide-sequence
  • cap-snatching mechanism
  • open reading frame
  • messenger-rna
  • viral-rna
  • 5' ends
  • base complementarity
  • neuraminidase gene
  • alpha-amanitin

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