tetano
Editor, Senior Moderator
Vet Microbiol
. 2023 Apr 25;282:109760.
doi: 10.1016/j.vetmic.2023.109760. Online ahead of print. Comprehensive analysis of the key amino acid substitutions in the polymerase and NP of avian influenza virus that enhance polymerase activity and affect adaptation to mammalian hosts
Yanna Guo[SUP] 1 [/SUP], Tongtong Sun[SUP] 1 [/SUP], Xuebing Bai[SUP] 1 [/SUP], Bing Liang[SUP] 1 [/SUP], Lulu Deng[SUP] 1 [/SUP], Yiqing Zheng[SUP] 1 [/SUP], Mengqi Yu[SUP] 1 [/SUP], Yinjing Li[SUP] 1 [/SUP], Jihui Ping[SUP] 2 [/SUP]
Affiliations
Accumulation of adaptive mutations in the polymerase and NP genes is crucial for the adaptation of avian influenza A viruses (IAV) to a new host. Here, we identified residues in the polymerase and NP proteins for which the percentages were substantially different between avian and human influenza viruses, to screen for key mammalian adaptive markers. The top 10 human virus-like residues in each gene segment were then selected for analysis of polymerase activity. Our research revealed that the PA-M311I and PA-A343S mutations increased the polymerase activity among the 40 individual mutations that augmented viral transcription and genomic replication, leading to increased virus yields, pro-inflammatory cytokine/chemokine levels and pathogenicity in mice. We also investigated the accumulative mutations in multiple polymerase genes and discovered that a combination of PB2-E120D/V227I, PB1-K52R/L212V/R486K/V709I, PA-R204K/M311I, and NP-E18D/R65K (hereafter referred to as the ten-sites joint mutations) has been identified to generate the highest polymerase activity, which can to some extent make up for the highest polymerase activity caused by the PB2-627 K mutation. When the ten-sites joint mutations co-occur with 627 K, the polymerase activity was further enhanced, potentially resulting in a virus with an improved phenotype that can infect a broader range of hosts, including mammals. This could lead to a greater public health concern than the current epidemic, highlighting that continuous surveillance of the variations of these sites is utmost important.
Keywords: Influenza A virus; Mammalian adaptation; Pathogenicity; Polymerase activity.
. 2023 Apr 25;282:109760.
doi: 10.1016/j.vetmic.2023.109760. Online ahead of print. Comprehensive analysis of the key amino acid substitutions in the polymerase and NP of avian influenza virus that enhance polymerase activity and affect adaptation to mammalian hosts
Yanna Guo[SUP] 1 [/SUP], Tongtong Sun[SUP] 1 [/SUP], Xuebing Bai[SUP] 1 [/SUP], Bing Liang[SUP] 1 [/SUP], Lulu Deng[SUP] 1 [/SUP], Yiqing Zheng[SUP] 1 [/SUP], Mengqi Yu[SUP] 1 [/SUP], Yinjing Li[SUP] 1 [/SUP], Jihui Ping[SUP] 2 [/SUP]
Affiliations
- PMID: 37120967
- DOI: 10.1016/j.vetmic.2023.109760
Accumulation of adaptive mutations in the polymerase and NP genes is crucial for the adaptation of avian influenza A viruses (IAV) to a new host. Here, we identified residues in the polymerase and NP proteins for which the percentages were substantially different between avian and human influenza viruses, to screen for key mammalian adaptive markers. The top 10 human virus-like residues in each gene segment were then selected for analysis of polymerase activity. Our research revealed that the PA-M311I and PA-A343S mutations increased the polymerase activity among the 40 individual mutations that augmented viral transcription and genomic replication, leading to increased virus yields, pro-inflammatory cytokine/chemokine levels and pathogenicity in mice. We also investigated the accumulative mutations in multiple polymerase genes and discovered that a combination of PB2-E120D/V227I, PB1-K52R/L212V/R486K/V709I, PA-R204K/M311I, and NP-E18D/R65K (hereafter referred to as the ten-sites joint mutations) has been identified to generate the highest polymerase activity, which can to some extent make up for the highest polymerase activity caused by the PB2-627 K mutation. When the ten-sites joint mutations co-occur with 627 K, the polymerase activity was further enhanced, potentially resulting in a virus with an improved phenotype that can infect a broader range of hosts, including mammals. This could lead to a greater public health concern than the current epidemic, highlighting that continuous surveillance of the variations of these sites is utmost important.
Keywords: Influenza A virus; Mammalian adaptation; Pathogenicity; Polymerase activity.