The R251K Substitution in Viral Protein PB2 Increases Viral Replication and Pathogenicity of Eurasian Avian-like H1N1 Swine Influenza Viruses
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...
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MDPI AG
2020-01-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/12/1/52 |
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| author | Mengkai Cai Ruting Zhong Chenxiao Qin Zhiqing Yu Xiaoyan Wen Junsi Xian Yongjie Chen Yu Cai Heyou Yi Lang Gong Guihong Zhang |
| author_facet | Mengkai Cai Ruting Zhong Chenxiao Qin Zhiqing Yu Xiaoyan Wen Junsi Xian Yongjie Chen Yu Cai Heyou Yi Lang Gong Guihong Zhang |
| author_sort | Mengkai Cai |
| collection | DOAJ |
| description | 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 <i>PB2</i> 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. |
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| id | doaj.art-f6b85c102c0247e49650ebe3d994ab6a |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-04-13T04:41:58Z |
| publishDate | 2020-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-f6b85c102c0247e49650ebe3d994ab6a2022-12-22T03:01:58ZengMDPI AGViruses1999-49152020-01-011215210.3390/v12010052v12010052The R251K Substitution in Viral Protein PB2 Increases Viral Replication and Pathogenicity of Eurasian Avian-like H1N1 Swine Influenza VirusesMengkai Cai0Ruting Zhong1Chenxiao Qin2Zhiqing Yu3Xiaoyan Wen4Junsi Xian5Yongjie Chen6Yu Cai7Heyou Yi8Lang Gong9Guihong Zhang10College of Veterinary Medicine, South China Agricultural University, Guangzhou 510462, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou 510462, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou 510462, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou 510462, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou 510462, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou 510462, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou 510462, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou 510462, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou 510462, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou 510462, ChinaCollege of Veterinary Medicine, South China Agricultural University, Guangzhou 510462, ChinaThe 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 <i>PB2</i> 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.https://www.mdpi.com/1999-4915/12/1/52eurasian avian-like h1n1 swine influenza viruses<i>pb2</i> genepb2-r251kpathogenicitypolymerase |
| spellingShingle | Mengkai Cai Ruting Zhong Chenxiao Qin Zhiqing Yu Xiaoyan Wen Junsi Xian Yongjie Chen Yu Cai Heyou Yi Lang Gong Guihong Zhang The R251K Substitution in Viral Protein PB2 Increases Viral Replication and Pathogenicity of Eurasian Avian-like H1N1 Swine Influenza Viruses Viruses eurasian avian-like h1n1 swine influenza viruses <i>pb2</i> gene pb2-r251k pathogenicity polymerase |
| title | The R251K Substitution in Viral Protein PB2 Increases Viral Replication and Pathogenicity of Eurasian Avian-like H1N1 Swine Influenza Viruses |
| title_full | The R251K Substitution in Viral Protein PB2 Increases Viral Replication and Pathogenicity of Eurasian Avian-like H1N1 Swine Influenza Viruses |
| title_fullStr | The R251K Substitution in Viral Protein PB2 Increases Viral Replication and Pathogenicity of Eurasian Avian-like H1N1 Swine Influenza Viruses |
| title_full_unstemmed | The R251K Substitution in Viral Protein PB2 Increases Viral Replication and Pathogenicity of Eurasian Avian-like H1N1 Swine Influenza Viruses |
| title_short | The R251K Substitution in Viral Protein PB2 Increases Viral Replication and Pathogenicity of Eurasian Avian-like H1N1 Swine Influenza Viruses |
| title_sort | r251k substitution in viral protein pb2 increases viral replication and pathogenicity of eurasian avian like h1n1 swine influenza viruses |
| topic | eurasian avian-like h1n1 swine influenza viruses <i>pb2</i> gene pb2-r251k pathogenicity polymerase |
| url | https://www.mdpi.com/1999-4915/12/1/52 |
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