Risk Assessment on lung injury and transmission potential of influenza viruses using in vitro and ex vivo models of human respiratory tract.

Abstract

Introduction: Preparation for influenza pandemics remains a public health challenge and risk assessment of influenza viruses is key to tackle this. Current risk assessment tools evaluate the properties, population and ecology of a virus. While acute lung injury (ALI) has been the main cause of deaths of highly pathogenic avian influenza (HPAI) viruses, like H5N1, there is limited risk assessment tool to evaluate the potential of virus to cause ALI. Different influenza virus strains infect and replicate in human respiratory tract differently to affect the pathogenicity and transmission potential. However, this cannot distinguish the disease severity of different virus strains. Previously, we have used a physiologically relevant in vitro ALI model to distinguish the ability of H5N1 and H1N1 viruses to cause ALI through measuring the rate of alveolar fluid clearance (AFC). We proposed to use this in vitro model to risk assess the ability of different influenza virus subtypes to cause ALI, as well as ex vivo explant culture of human respiratory tract to evaluate virus pathogenicity and transmission potential. Method: Primary culture of human alveolar epithelial cells in a transwell and human lung and bronchus explants were infected with different influenza virus subtypes (including avian surveillance isolates). AFC, virus infectivity and replication of ex vivo explants were measured. Result: We found that H1N1, H3N2, H5N1, H5N6 and H7N9 have differential viral replication in human lungs. HPAI H5N1 and H7N9 induced severe AFC impairment compare to seasonal influenza A and influenza B viruses. High preference of bronchus tropism was found in seasonal and pandemic H1N1 viruses but minimal in HPAI H5N1 viruses. Conclusion: In summary, evaluation of virus-induced lung injury can differentiate the ability of viruses to cause severe disease in humans, which in addition enhances the risk assessment of animal influenza viruses identified from ongoing surveillance.