tetano
Editor, Senior Moderator
Viruses. 2020 Jan 2;12(1). pii: E52. doi: 10.3390/v12010052. [h=1]The R251K Substitution in Viral Protein PB2 Increases Viral Replication and Pathogenicity of Eurasian Avian-like H1N1 Swine Influenza Viruses.[/h]
Cai M[SUP]1,[/SUP][SUP]2[/SUP], Zhong R[SUP]1,[/SUP][SUP]3[/SUP], Qin C[SUP]1,[/SUP][SUP]2[/SUP], Yu Z[SUP]1,[/SUP][SUP]2[/SUP], Wen X[SUP]1,[/SUP][SUP]2[/SUP], Xian J[SUP]1,[/SUP][SUP]2[/SUP], Chen Y[SUP]1,[/SUP][SUP]2[/SUP], Cai Y[SUP]1,[/SUP][SUP]2[/SUP], Yi H[SUP]1,[/SUP][SUP]2[/SUP], Gong L[SUP]1,[/SUP][SUP]2[/SUP], Zhang G[SUP]1,[/SUP][SUP]2[/SUP].
[h=3]Author information[/h] 1 College of Veterinary Medicine, South China Agricultural University, Guangzhou 510462, China. 2 Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, South China Agricultural University, Guangzhou 510462, China. 3 National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou 510462, China.
[h=3]Abstract[/h] The Eurasian avian-like swine (EA) H1N1 virus has affected the Chinese swine industry, and human infection cases have been reported occasionally. However, little is known about the pathogenic mechanism of EA H1N1 virus. In this study, we compared the mouse pathogenicity of A/swine/Guangdong/YJ4/2014 (YJ4) and A/swine/Guangdong/MS285/2017 (MS285) viruses, which had similar genotype to A/Hunan/42443/2015 (HuN-like). None of the mice inoculated with 10[SUP]6[/SUP] TCID[SUB]50[/SUB] of YJ4 survived at 7 days post infection, while the survival rate of the MS285 group was 100%. Therefore, a series of single fragment reassortants in MS285 background and two rescued wild-type viruses were generated by using the reverse genetics method, and the pathogenicity analysis revealed that the PB2 gene contributed to the high virulence of YJ4 virus. Furthermore, there were 11 amino acid differences in PB2 between MS285 and YJ4 identified by sequence alignment, and 11 single amino acid mutant viruses were generated in the MS285 background. We found that the R251K mutation significantly increased the virulence of MS285 in mice, contributed to high polymerase activity and enhanced viral genome transcription and replication. These results indicate that PB2-R251K contributes to the virulence of the EA H1N1 virus and provide new insight into future molecular epidemiological surveillance strategies.
[h=4]KEYWORDS:[/h] Eurasian avian-like H1N1 swine influenza viruses; PB2 gene; PB2-R251K; pathogenicity; polymerase
PMID: 31906472 DOI: 10.3390/v12010052
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Cai M[SUP]1,[/SUP][SUP]2[/SUP], Zhong R[SUP]1,[/SUP][SUP]3[/SUP], Qin C[SUP]1,[/SUP][SUP]2[/SUP], Yu Z[SUP]1,[/SUP][SUP]2[/SUP], Wen X[SUP]1,[/SUP][SUP]2[/SUP], Xian J[SUP]1,[/SUP][SUP]2[/SUP], Chen Y[SUP]1,[/SUP][SUP]2[/SUP], Cai Y[SUP]1,[/SUP][SUP]2[/SUP], Yi H[SUP]1,[/SUP][SUP]2[/SUP], Gong L[SUP]1,[/SUP][SUP]2[/SUP], Zhang G[SUP]1,[/SUP][SUP]2[/SUP].
[h=3]Author information[/h] 1 College of Veterinary Medicine, South China Agricultural University, Guangzhou 510462, China. 2 Key Laboratory of Zoonosis Prevention and Control of Guangdong Province, South China Agricultural University, Guangzhou 510462, China. 3 National Engineering Research Center for Breeding Swine Industry, South China Agricultural University, Guangzhou 510462, China.
[h=3]Abstract[/h] The Eurasian avian-like swine (EA) H1N1 virus has affected the Chinese swine industry, and human infection cases have been reported occasionally. However, little is known about the pathogenic mechanism of EA H1N1 virus. In this study, we compared the mouse pathogenicity of A/swine/Guangdong/YJ4/2014 (YJ4) and A/swine/Guangdong/MS285/2017 (MS285) viruses, which had similar genotype to A/Hunan/42443/2015 (HuN-like). None of the mice inoculated with 10[SUP]6[/SUP] TCID[SUB]50[/SUB] of YJ4 survived at 7 days post infection, while the survival rate of the MS285 group was 100%. Therefore, a series of single fragment reassortants in MS285 background and two rescued wild-type viruses were generated by using the reverse genetics method, and the pathogenicity analysis revealed that the PB2 gene contributed to the high virulence of YJ4 virus. Furthermore, there were 11 amino acid differences in PB2 between MS285 and YJ4 identified by sequence alignment, and 11 single amino acid mutant viruses were generated in the MS285 background. We found that the R251K mutation significantly increased the virulence of MS285 in mice, contributed to high polymerase activity and enhanced viral genome transcription and replication. These results indicate that PB2-R251K contributes to the virulence of the EA H1N1 virus and provide new insight into future molecular epidemiological surveillance strategies.
[h=4]KEYWORDS:[/h] Eurasian avian-like H1N1 swine influenza viruses; PB2 gene; PB2-R251K; pathogenicity; polymerase
PMID: 31906472 DOI: 10.3390/v12010052
Free full text