Analysis of the risk of evolution from low to highly pathogenic avian influenza virus – RISKEVOL

Highly Pathogenic Avian Influenza Viruses (HPAIV) evolve from Low Pathogenic viruses (LPAIV) through a process involving nucleotide substitutions and nucleotide insertions in the sequence encoding the viral hemagglutinin (HA), resulting in the apparition of a stretch of basic amino-acids at the HA proteolytic cleavage site. Only viruses with H5 and H7 HA have been recorded to evolve into HPAIV, most likely due to some distinctive properties of their HA genes, be it the nucleotide sequence of the HA segment or its folded structure that may somehow favour the substitutions or additions of nucleotides in the sequence encoding the HA cleavage site. For a given H5 or H7 LPAIV, the risk of evolution to a HPAIV is currently unknown. The aim of this project is to analyse to what extent and by which mechanisms the HA nucleotide sequence may modulate the evolution towards the acquisition of a polybasic HA cleavage site and to ultimately predict the risk of LPAIV evolution to a HPAIV.