Secondary Structure of Influenza A Virus Genomic Segment 8 RNA Folded in a Cellular Environment

Int J Mol Sci. 2022 Feb 23;23(5):2452. doi: 10.3390/ijms23052452.


Influenza A virus (IAV) is a member of the single-stranded RNA (ssRNA) family of viruses. The most recent global pandemic caused by the SARS-CoV-2 virus has shown the major threat that RNA viruses can pose to humanity. In comparison, influenza has an even higher pandemic potential as a result of its high rate of mutations within its relatively short (<13 kbp) genome, as well as its capability to undergo genetic reassortment. In light of this threat, and the fact that RNA structure is connected to a broad range of known biological functions, deeper investigation of viral RNA (vRNA) structures is of high interest. Here, for the first time, we propose a secondary structure for segment 8 vRNA (vRNA8) of A/California/04/2009 (H1N1) formed in the presence of cellular and viral components. This structure shows similarities with prior in vitro experiments. Additionally, we determined the location of several well-defined, conserved structural motifs of vRNA8 within IAV strains with possible functionality. These RNA motifs appear to fold independently of regional nucleoprotein (NP)-binding affinity, but a low or uneven distribution of NP in each motif region is noted. This research also highlights several accessible sites for oligonucleotide tools and small molecules in vRNA8 in a cellular environment that might be a target for influenza A virus inhibition on the RNA level.

Keywords: IAV; RNA chemical mapping; RNA secondary structure; RNA virus; influenza A virus.

MeSH terms

  • Animals
  • Base Sequence
  • Dogs
  • Gene Expression Regulation, Viral*
  • Genome, Viral / genetics*
  • Humans
  • Influenza A Virus, H1N1 Subtype / genetics*
  • Influenza A Virus, H1N1 Subtype / metabolism
  • Influenza, Human / virology
  • Madin Darby Canine Kidney Cells
  • Models, Molecular
  • Nucleic Acid Conformation*
  • Nucleotide Motifs / genetics
  • RNA Folding
  • RNA, Viral / chemistry*
  • RNA, Viral / genetics
  • Viral Proteins / genetics
  • Viral Proteins / metabolism


  • RNA, Viral
  • Viral Proteins