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.
Bibliographical noteFunding Information:
This work was supported by National Institute of Allergy and Infectious Diseases, National Institutes of Health (NIAID/NIH) contract HHSN272201400008C. This work has also received funding from the European Union's Horizon 2020 research and innovation program under DELTA-FLU, grant agreement no. 727922. We gratefully acknowledge the originating and submitting laboratories for sequences in the GISAID’s EpiFlu Database, used in this study.
© 2021 Gultyaev et al.