Prediction of the next highly pathogenic avian influenza pandemic that can cause illness in humans

Background:In recent years,avian influenza viruses(AIVs)have seriously threatened human health.Questions such as:why do AIVs infect humans?,how quickly can an AIV become pandemic?,and which virus is the most dangerous?cannot be sufficiently answered using current bioinformatic studies.Method:Secondary structures and energies of representative 5′-untranslated region(UTR)of the HA gene were calculated.Then their secondary structures and energies were re-calculated after one or two nucleotide substitutions were introduced into the HA 5′-UTR.Phylogenetic trees on the basis of hemagglutinin(HA)and polymerase basic protein 2(PB2)amino acid sequences and HA 5′-UTR nucleotide sequences were constructed.The connection between the energy and translation efficiency of 5′-UTR was confirmed by in vitro coupled transcription/translation assay.Results:The simplicity of the secondary structure of the 5′-UTR of the HA gene determines the overall virus replication rate and transmission potential.Point mutation assays show that the 5′-UTR sequences of the HA gene in the influenza subtypes H2N2,H3N2,and H7N9 have greater variation potentials than other virus subtypes.Conclusion:Some high-virulent strains of avian influenza might emerge in the next two to three years.The H2N2 subtype,once disappeared in humans,may stage a comeback.The current outbreak of H7N9 may become pandemic and cause even more deaths,if one or two bases are substituted in the 5′-UTR sequence of the HA gene.