Abstract
Subtype H6 avian influenza A viruses (IAVs) are enzootic and genetically diverse in both domestic poultry and wild waterfowl and may cause spillovers in both pigs and humans. Thus, it is important to understand the genetic diversity of H6 IAVs in birds and their zoonotic potential. Compared with that in domestic poultry, the genetic diversity of H6 viruses in wild birds in China has not been well-understood. In this study, five H6 viruses were isolated from wild birds in Poyang Lake, China, and genetic analyses showed that these isolates are clustered into four genotypes associated with reassortments among avian IAVs from domestic poultry and wild birds in China and those from Eurasia and North America and that these viruses exhibited distinct phenotypes in growth kinetics analyses with avian and mammalian cells lines and in mouse challenge experiments. Of interest is that two H6 isolates from the Eurasian teal replicated effectively in the mouse lung without prior adaptation, whereas the other three did not. Our study suggested that there are variations in the mammalian viral replication efficiency phenotypic among genetically diverse H6 IAVs in wild birds and that both intra- and inter-continental movements of IAVs through wild bird migration may facilitate the emergence of novel H6 IAV reassortants with the potential for replicating in mammals, including humans. Continued surveillance to monitor the diversity of H6 IAVs in wild birds is necessary to increase our understanding of the natural history of IAVs.
Highlights
The influenza A virus (IAV) belongs to the Orthomyxoviridae family and contains a genome with eight negative sense, single-stranded RNA segments
The HA genes from E-Teal/417 and GWF-Goose/740 were genetically associated with a bean goose isolate [A/Bean Goose/South Korea/KNU18 6/2018 (H6N5)] and H6 IAVs circulated in the wild bird population from North America, which were initially introduced from Eurasia to North America perhaps in the late 1990s through intercontinental bird migration and caused outbreaks in domestic poultry in California from 2000 to 2005 (Figure 1A and Supplementary Figure S1) [10, 11, 34]
The HA genes of E-Wigeon/158 and EWigeon/266 were genetically close to H6 viruses circulating in domestic poultry in Southeast China and two avian-origin H6N6 swine IAVs [24, 35], whereas that of E-Teal/49 was genetically close to the HA of H6 viruses circulating in the wild bird population across Eurasia (Figure 1A) and share the same ancestor with A/chicken/Zhejiang/1667/2017 (H6N1)
Summary
The influenza A virus (IAV) belongs to the Orthomyxoviridae family and contains a genome with eight negative sense, single-stranded RNA segments. It is important to differentiate typical and atypical influenza occurrences in waterfowl, especially among the interfaces among wild birds, domestic animals, and humans, which provide frontiers for the emergence of potential pandemic IAVs. Since its first isolation from a turkey in the United States in 1965 [4], subtype H6 avian IAVs have been identified in various migratory waterfowl and domestic poultry in Eurasia and North America [5] and contributed to the genomic exchange and diversity of IAVs in wild birds [2, 6,7,8,9]. H6 IAVs have been isolated from wild birds in China [16, 18], the genetic diversity of H6 IAVs in wild birds in China is not well-understood
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