The Novel Human Influenza A(H7N9) Virus Is Naturally Adapted to Efficient Growth in Human Lung Tissue

J.K. and K.L.S. contributed equally to this work. ABSTRACT A novel influenza A virus (IAV) of the H7N9 subtype has been isolated from severely diseased patients with pneumo-nia and acute respiratory distress syndrome and, apparently, from healthy poultry inMarch 2013 in Eastern China. We evalu-ated replication, tropism, and cytokine induction of the A/Anhui/1/2013 (H7N9) virus isolated from a fatal human infection and two low-pathogenic avian H7 subtype viruses in a human lung organ culture systemmimicking infection of the lower respira-tory tract. The A(H7N9) patient isolate replicated similarly well as a seasonal IAV in explanted human lung tissue, whereas avian H7 subtype viruses propagated poorly. Interestingly, the avian H7 strains provoked a strong antiviral type I interferon (IFN-I) response, whereas the A(H7N9) virus induced only low IFN levels. Nevertheless, all viruses analyzed were detected predomi-nantly in type II pneumocytes, indicating that the A(H7N9) virus does not differ in its cellular tropism from other avian or hu-man influenza viruses. Tissue culture-based studies suggested that the low induction of the IFN- promoter correlated with an efficient suppression by the viral NS1 protein. These findings demonstrate that the zoonotic A(H7N9) virus is unusually well adapted to efficient propagation in human alveolar tissue, which most likely contributes to the severity of lower respiratory trac