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

bioRxiv (Cold Spring Harbor Laboratory)

Abstract

ABSTRACT 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 multi basic 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.

Authors 5

1. Alexander P. Gultyaev corresponding Aachen Group Imaging and Bioinformatics Leiden Institute of Advanced Computer Science

   Leiden University · Erasmus MC

   Affiliation as printed

   Department of Viroscience, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, the Netherlands

   Group Imaging and Bioinformatics, Leiden Institute of Advanced Computer Science (LIACS), Leiden University, P.O. Box 9512, 2300 RA Leiden, the Netherlands

   Group Imaging and Bioinformatics, Leiden Institute of Advanced Computer Science (LIACS), Leiden University, P.O. Box 951, 300 RA Leiden, the Netherlands

2. Monique I. J. Spronken

   Erasmus MC

   Affiliation as printed

   Department of Viroscience, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, the Netherlands

3. Mathis Funk

   Erasmus MC

   Affiliation as printed

   Department of Viroscience, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, the Netherlands

4. Ron A. M. Fouchier

   Erasmus MC

   Affiliation as printed

   Department of Viroscience, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, the Netherlands

5. Mathilde Richard corresponding

   Erasmus MC

   Affiliation as printed

   Department of Viroscience, Erasmus Medical Center, P.O. Box 2040, 3000 CA Rotterdam, the Netherlands