tetano
Editor, Senior Moderator
Poult Sci
. 2025 Jan 18;104(2):104832.
doi: 10.1016/j.psj.2025.104832. Online ahead of print. Hemagglutinin with a polybasic cleavage site confers high virulence on H7N9 avian influenza viruses
Jinyuan Gu[SUP] 1 [/SUP], Yayao Yan[SUP] 2 [/SUP], Zixiong Zeng[SUP] 2 [/SUP], Dong Liu[SUP] 2 [/SUP], Jiao Hu[SUP] 3 [/SUP], Shunlin Hu[SUP] 3 [/SUP], Xiaoquan Wang[SUP] 3 [/SUP], Min Gu[SUP] 4 [/SUP], Xiufan Liu[SUP] 5 [/SUP]
Affiliations
H7N9 avian influenza virus (AIV) first emerged in February 2013 in China, and early isolates were all low pathogenic (LP). After circulation for a few years in live poultry markets of China, LP H7N9 AIVs evolved into a highly pathogenic (HP) form in late 2016. Deduced amino acid sequence analysis of hemagglutinin (HA) gene revealed that all HP H7N9 AIVs have obtained four-amino-acid insertion at position 339-342 (H7 numbering), making the cleavage site from a monobasic motif (LP AIVs) to a polybasic form (HP AIVs). Notably, the polybasic cleavage site motifs are diversified, of which PEVPKRKRTAR↓GLF motif is prevalent. To elucidate the reasons accounting for its dominance, recombinant H7N9 virus carrying PEVPKRKRTAR↓GLF (rJT157-2) motif was generated based on LP H7N9 virus A/chicken/Eastern China/JT157/2016 (JT157). Besides, another two viruses containing PEVPKGKRTAR↓GLF (rJT157-1) and PEIPKRKRTAR↓GLF (rJT157-3) cleavage site motifs were also constructed as comparisons. We found that rJT157-2 showed better biological characterizations in vitro including replication kinetics, plaque size, thermal and acid stability. In addition, animal experiments demonstrated that rJT157-2 was more pathogenic to both chickens and mice with higher virus titers and induced more severe changes in the lungs. These results suggested that HP H7N9 viruses carrying PEVPKRKRTAR↓GLF motif in the HA cleavage site were most likely adaptive mutants during the evolution of H7N9 AIVs.
Keywords: H7N9 avian influenza virus; adaptive mutants; highly pathogenic; low pathogenic; polybasic cleavage sites.
. 2025 Jan 18;104(2):104832.
doi: 10.1016/j.psj.2025.104832. Online ahead of print. Hemagglutinin with a polybasic cleavage site confers high virulence on H7N9 avian influenza viruses
Jinyuan Gu[SUP] 1 [/SUP], Yayao Yan[SUP] 2 [/SUP], Zixiong Zeng[SUP] 2 [/SUP], Dong Liu[SUP] 2 [/SUP], Jiao Hu[SUP] 3 [/SUP], Shunlin Hu[SUP] 3 [/SUP], Xiaoquan Wang[SUP] 3 [/SUP], Min Gu[SUP] 4 [/SUP], Xiufan Liu[SUP] 5 [/SUP]
Affiliations
- PMID: 39862488
- DOI: 10.1016/j.psj.2025.104832
H7N9 avian influenza virus (AIV) first emerged in February 2013 in China, and early isolates were all low pathogenic (LP). After circulation for a few years in live poultry markets of China, LP H7N9 AIVs evolved into a highly pathogenic (HP) form in late 2016. Deduced amino acid sequence analysis of hemagglutinin (HA) gene revealed that all HP H7N9 AIVs have obtained four-amino-acid insertion at position 339-342 (H7 numbering), making the cleavage site from a monobasic motif (LP AIVs) to a polybasic form (HP AIVs). Notably, the polybasic cleavage site motifs are diversified, of which PEVPKRKRTAR↓GLF motif is prevalent. To elucidate the reasons accounting for its dominance, recombinant H7N9 virus carrying PEVPKRKRTAR↓GLF (rJT157-2) motif was generated based on LP H7N9 virus A/chicken/Eastern China/JT157/2016 (JT157). Besides, another two viruses containing PEVPKGKRTAR↓GLF (rJT157-1) and PEIPKRKRTAR↓GLF (rJT157-3) cleavage site motifs were also constructed as comparisons. We found that rJT157-2 showed better biological characterizations in vitro including replication kinetics, plaque size, thermal and acid stability. In addition, animal experiments demonstrated that rJT157-2 was more pathogenic to both chickens and mice with higher virus titers and induced more severe changes in the lungs. These results suggested that HP H7N9 viruses carrying PEVPKRKRTAR↓GLF motif in the HA cleavage site were most likely adaptive mutants during the evolution of H7N9 AIVs.
Keywords: H7N9 avian influenza virus; adaptive mutants; highly pathogenic; low pathogenic; polybasic cleavage sites.