Characteristics of stork feces‐derived H5N1 viruses that are preferentially transmitted to primary human airway epithelial cells

Avian influenza viruses are a possible threat to human health as they may cause an influenza pandemic. Asian open‐bill storks are migratory birds that brought H5N1 viruses into Thailand during the 2004–2005 epidemic. However, to date, there are no reports of direct transmission of stork‐derived H5N1 viruses to Thais. Therefore, we questioned whether or not H5N1 viruses secreted in the feces of infected storks could directly infect cells derived from the human respiratory tract. To answer this question, we used primary NHBE cells as a model. We found that H5N1 viruses from two of the three cloacal swabs rapidly replicated and caused severe structural damage to the infected NHBE cells within the early phase of infection. Viruses from the remaining swab replicated poorly and caused no damage to the infected cells. The rapid‐replicating viruses were able to replicate efficiently even in the presence of a high level of type I IFN production and stimulated a high level of IL‐6 production but not the immunosuppressive cytokine, IL‐10. The genotypic study revealed that the major genotypes of the two rapid‐replicating viruses present in stork feces were the best‐fit genotypes for replication in the primary NHBE cells. In contrast, the major NA‐based genotype found in the cloacal swab containing slow‐replicating viruses could not survive in the primary NHBE cells. Altogether, the data suggested that those stork‐derived H5N1 viruses that preferentially replicated in human airway epithelial cells may exist in nature, and may not require additional mutations in order to defeat the species barrier.