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J Thorac Dis
. 2021 Aug;13(8):4650-4660.
doi: 10.21037/jtd-21-226.
Multiple basic amino acids in the cleavage site of H7N9 hemagglutinin contribute to high virulence in mice
Wenjun Song 1 2 , Xiaofeng Huang 2 , Wenda Guan 1 , Pin Chen 2 , Pui Wang 2 , Min Zheng 2 , Zhengtu Li 1 , Yutao Wang 1 , Zifeng Yang 1 , Honglin Chen 2 , Xinhua Wang 1
Affiliations
- PMID: 34527306
- PMCID: PMC8411188
- DOI: 10.21037/jtd-21-226
Abstract
Background: Avian influenza A (H7N9) virus has caused more than 1,500 cases of human infection since its emergence in early 2013. Displaying little or no pathogenicity in poultry, but a 40% case-fatality rate in humans, five waves of H7N9 human infections occurred in China during 2013-2017, caused solely by a low pathogenicity strain. However, avian isolates possessing a polybasic connecting peptide in the hemagglutinin (HA) protein were detected in mid-2016, indicating that a highly pathogenic virus had emerged and was co-circulating with the low pathogenicity strains.
Methods: Here we characterize the pathogenicity of a newly emerged human H7N9 variant with a PEVPKRKRTAR/GLF insertion motif at the cleavage site of the HA protein in vitro and in vivo.
Results: This variant replicates in MDCK cells independently of TPCK-trypsin, which is indicative of high pathogenicity in chickens. The 50% mouse lethal dose (MLD50) of this novel isolate was less than 10 plaque forming units (PFU), compared with 3.16×104 for an identical virus lacking the polybasic insertion, indicating a high virulence phenotype.
Conclusions: Our results demonstrate that the multiple basic amino acid insertion in the HA protein of the H7N9 variant confers high virulence in mammals, highlighting a potential risk to humans. Continuous viral surveillance is therefore necessary in the China region to improve pandemic preparedness.
Keywords: H7N9; Influenza A virus (IAV); cleavage site; highly pathogenic avian influenza (HPAI); polybasic connecting peptide.