Abstract Title
The risk of evolution to HPAIV is determined by the primary sequences of the HA cleavage site
Abstract
High pathogenicity avian influenza viruses (HPAIV) emerge from H5 and H7 low pathogenicity avian influenza virus (LPAIV) progenitors through mutations that introduce a multibasic cleavage site (MBCS) in the HA. The genetic mechanism underlying this evolutionary process is poorly characterized, and some major questions remain unanswered. Have all LPAIV the same probability of evolving towards HPAIV? Are there specific features on the HA genomic segment that can influence the risk to evolve to HPAIV? To address these questions, we developed an original experimental system allowing to grow a virus with an HA freed from selection pressure on protein function and used a sequencing-error correcting strategy followed by innovative bioinformatics analyses to determine the mechanisms of MBCS acquisition in H5 viruses. A thorough investigation of a diversity of H5 HPAIV emergence events demonstrated that the insertion of nucleotides in the HA cleavage site is due to polymerase back-tracking. Furthermore, we demonstrate that the risk of nucleotide insertion is solely dependent on the thermodynamic stability of the product-template interaction within the polymerase catalytic site. We identify potential transient intermediates between LPAIV and HPAIV, which display highly evolable H5 sequences.
Co-Author(s)
Bertille Pouget1, Aldair Martinez-Pineda1,2, Gabriel Dupre1, Claire Hoede2, Christine Gaspin2, Roland Marquet3, Romain Volmer1
1 Ecole Nationale Vétérinaire de Toulouse, Université de Toulouse, ENVT, INRAE, IHAP, UMR 1225, Toulouse, France.
2 Université de Toulouse, INRAE, UR MIAT, 31326, Castanet-Tolosan, France
3 Université de Strasbourg, CNRS, Architecture et Réactivité de l'ARN, UPR9002, 67000 Strasbourg, France.
Abstract Category
Avian influenza in mammals, pandemic preparedness, and one health