A 2022 avian H5N1 influenza A virus from clade 2.3.4.4b attaches to and replicates better in human respiratory epithelium than a 2005 H5N1 virus from clade 2.3.2.1
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Background
Highly pathogenic avian influenza (HPAI) H5 viruses of the A/Goose/Guangdong/1/1996 (GsGd) lineage pose significant global risks to wildlife, domestic animals, and humans. Recent cross-species transmission events to mammals, including humans, highlight this risk. Critical determinants for cross-species and intra-species transmission include the ability to attach to and replicate in respiratory epithelial cells. Although these factors have been studied for HPAI H5N1 viruses in the past, limited studies are available for currently circulating strains.
Methods
We compared level of adaptation to human respiratory tract of a HPAI H5N1 clade 2.3.4.4b (H5N1 2022 ) virus with those of well characterized HPAI H5N1 clade 2.1.3.2 (H5N1 2005 ) and seasonal H3N2 2003 viruses by three methods. First, we compared pattern of virus attachment by virus histochemistry. Second, we compared efficiency of infection and replication, as well as innate immune responses in human respiratory epithelium in vitro . Lastly, we compared polymerase complex activity in a minigenome assay.
Findings
The H5N1 2022 virus attached more abundantly to and replicated more efficiently in cells of the human respiratory tract compared to H5N1 2005 and H3N2 viruses. This increased replication was not associated with an increased polymerase activity of H5N1 2022 virus compared to H3N2 2003 virus. The efficient replication of H5N1 2022 virus infection induced a robust innate immune response almost comparable to H3N2 2003 .
Interpretation
The pattern of virus attachment and replication efficiency of a HPAI H5N1 2022 virus resembled that of H3N2 2003 virus more closely than a HPAI H5N1 2005 . This could contribute to an increased risk for both human infection and virus adaptations to humans.
Funding
The Netherlands Organization for Health Research and Development
Research in context
Evidence before this study
Highly pathogenic avian influenza (HPAI) H5 viruses of the A/Goose/Guangdong/1/1996 (GsGd) lineage (clade 2.3.4.4b) have the ability to spread to a wide range of domesticated and wild mammalian species, including humans. Cross species transmission and transmission among humans requires— among other factors—efficient infection of epithelial cells in the respiratory epithelium of the upper respiratory tract.
Added value of this study
In our study we show that a recent clade 2.3.4.4b HPAI H5N1 virus attached to and replicated more efficiently in respiratory epithelium than a clade 2.1.3.2 H5N1 virus that circulated in 2005.
Implications of all the available data
These data suggest that there might be an increased risk of human infections with the currently circulating 2.3.4.4b HPAI H5N1 viruses, which might facilitate opportunities for human adaptation.
