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Emerg Microbes Infect
. 2024 Sep 2:2400546.
doi: 10.1080/22221751.2024.2400546. Online ahead of print. The C-terminal amino acid motifs of NS1 protein affect the replication and virulence of naturally NS-truncated H1N1 canine influenza virus
Pingping Wang 1 2 3 , Jianing Guo 1 , Yefan Zhou 1 2 3 , Min Zhu 1 2 3 , Senbiao Fang 4 5 , Fanyuan Sun 1 2 3 , Chongqiang Huang 1 2 3 , Yaohui Zhu 1 2 3 , Huabo Zhou 6 , Boyu Pan 4 5 , Yifeng Qin 1 2 3 , Kang Ouyang 1 2 3 , Zuzhang Wei 1 2 3 , Weijian Huang 1 2 3 , Adolfo García-Sastre 7 8 9 , Ying Chen 1 2 3
Affiliations
AbstractThe vast majority of data obtained from sequence analysis of influenza A viruses (IAVs) have revealed that nonstructural 1 (NS1) proteins from H1N1 swine, H3N8 equine, H3N2 avian and the correspondent subtypes from dogs have a conserved four C-terminal amino acid motif when independent cross-species transmission occurs between these species. To test the influence of the C-terminal amino acid motifs of NS1 protein on the replication and virulence of IAVs, we systematically generated 7 recombinants, which carried naturally truncated NS1 proteins, and their last four C-terminal residues were replaced with PEQK and SEQK (for H1N1), EPEV and KPEI (for H3N8) and ESEV and ESEI (for H3N2) IAVs. Another recombinant was generated by removing the C-terminal residues by reverse genetics. Remarkably, the ESEI and KPEI motifs circulating in canines largely contributed efficient replication in cultured cells and these had enhanced virulence. In contrast, the avian ESEV motif was only responsible for high pathogenicity in mice. We examined the effects of these motifs upon interferon (IFN) induction. The 7 mutant viruses replicated in vitro in an IFN-independent manner, and the canine SEQK motif was able to induced higher levels of IFN-β in human cell lines. These findings shed further new light on the role of the four C-terminal residues in replication and virulence of IAVs and suggest that these motifs can modulate viral replication in a species-specific manner.
Keywords: Canine influenza virus; NS1 protein; four C-terminal residues; viral replication; virulence.
. 2024 Sep 2:2400546.
doi: 10.1080/22221751.2024.2400546. Online ahead of print. The C-terminal amino acid motifs of NS1 protein affect the replication and virulence of naturally NS-truncated H1N1 canine influenza virus
Pingping Wang 1 2 3 , Jianing Guo 1 , Yefan Zhou 1 2 3 , Min Zhu 1 2 3 , Senbiao Fang 4 5 , Fanyuan Sun 1 2 3 , Chongqiang Huang 1 2 3 , Yaohui Zhu 1 2 3 , Huabo Zhou 6 , Boyu Pan 4 5 , Yifeng Qin 1 2 3 , Kang Ouyang 1 2 3 , Zuzhang Wei 1 2 3 , Weijian Huang 1 2 3 , Adolfo García-Sastre 7 8 9 , Ying Chen 1 2 3
Affiliations
- PMID: 39221898
- DOI: 10.1080/22221751.2024.2400546
AbstractThe vast majority of data obtained from sequence analysis of influenza A viruses (IAVs) have revealed that nonstructural 1 (NS1) proteins from H1N1 swine, H3N8 equine, H3N2 avian and the correspondent subtypes from dogs have a conserved four C-terminal amino acid motif when independent cross-species transmission occurs between these species. To test the influence of the C-terminal amino acid motifs of NS1 protein on the replication and virulence of IAVs, we systematically generated 7 recombinants, which carried naturally truncated NS1 proteins, and their last four C-terminal residues were replaced with PEQK and SEQK (for H1N1), EPEV and KPEI (for H3N8) and ESEV and ESEI (for H3N2) IAVs. Another recombinant was generated by removing the C-terminal residues by reverse genetics. Remarkably, the ESEI and KPEI motifs circulating in canines largely contributed efficient replication in cultured cells and these had enhanced virulence. In contrast, the avian ESEV motif was only responsible for high pathogenicity in mice. We examined the effects of these motifs upon interferon (IFN) induction. The 7 mutant viruses replicated in vitro in an IFN-independent manner, and the canine SEQK motif was able to induced higher levels of IFN-β in human cell lines. These findings shed further new light on the role of the four C-terminal residues in replication and virulence of IAVs and suggest that these motifs can modulate viral replication in a species-specific manner.
Keywords: Canine influenza virus; NS1 protein; four C-terminal residues; viral replication; virulence.