Insertions of codons encoding basic amino acids in H7 hemagglutinins of influenza A viruses occur by recombination with RNA at hotspots near snoRNA binding sites

The presence of multiple basic amino acids in the protease cleavage site of the hemagglutinin (HA) protein is the main molecular determinant of virulence of highly pathogenic avian influenza (HPAI) viruses. Recombination of HA RNA with other RNA molecules of host or virus origin is a dominant mechanism of multibasic cleavage site (MBCS) acquisition for H7 subtype HA. Using alignments of HA RNA sequences from documented cases of MBCS insertion due to recombination, we show that such recombination with host RNAs is most likely to occur at particular hotspots in ribosomal RNAs (rRNAs), transfer RNAs (tRNAs), and viral RNAs. The locations of these hotspots in highly abundant RNAs indicate that RNA recombination is facilitated by the binding of small nucleolar RNA (snoRNA) near the recombination points.

Automated summary

Multiple basic amino acids at the protease cleavage site of HA protein play a key role in the virulence of highly pathogenic avian influenza viruses. Recombination of HA RNA with host RNAs, particularly at hotspots in rRNAs, tRNAs, and viral RNAs, is a dominant mechanism for acquiring MBCS in H7 subtype HPAI. The presence of small nucleolar RNAs near recombination points facilitates RNA recombination in highly abundant RNAs.