Assessing the fitness of distinct clades of influenza A (H9N2)viruses

Abstract

Influenza A (H9N2) viruses are a genetically diverse population that infects wild anddomestic avian species and mammals and contributed the internal gene segments to theA/H5N1 and A/H7N9 viruses associated with lethal human infections. Here we comprehensivelyassess the potential risk to mammals of a diverse panel of A/H9N2 viruses, representingthe major H9N2 clades, using a combination of in vitro assays (e.g.,antiviral susceptibility and virus growth in primary differentiated human airway cells)and in vivo assays (e.g., replication, transmission and/or pathogenicityof viruses in ducks, pigs, mice and ferrets). We observed that viruses isolated fromhumans, A/Hong Kong/1073/1999 and A/Hong Kong/33982/2009, had the highest risk potential.However, the A/swine/Hong Kong/9A-1/1998 and A/chicken/Hong Kong/G9/1997 viruses alsodisplayed several features suggesting a fitness profile adapted to human infection andtransmission. The North American avian H9N2 clade virus had the lowest risk profile, andthe other viruses tested displayed various levels of fitness across individual assays. Inmany cases, the known genotypic polymorphisms alone were not sufficient to accuratelypredict the virus’ phenotype. Therefore, we conclude that comprehensive riskanalyses based on surveillance of circulating influenza virus strains are necessary toassess the potential for human infection by emerging influenza A viruses.