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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Bibliographic Details
Published in:	Viruses Vol. 12; no. 1; p. 52
Main Authors:	Cai, Mengkai, Zhong, Ruting, Qin, Chenxiao, Yu, Zhiqing, Wen, Xiaoyan, Xian, Junsi, Chen, Yongjie, Cai, Yu, Yi, Heyou, Gong, Lang, Zhang, Guihong
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 02-01-2020 MDPI
Subjects:	A549 Cells Amino acid sequence Amino Acid Substitution Animals Dogs Epidemiology eurasian avian-like h1n1 swine influenza viruses Experiments Female Genomes Genotypes Humans Infections Influenza Influenza A Virus, H1N1 Subtype - genetics Influenza A Virus, H1N1 Subtype - pathogenicity Influenza A Virus, H1N1 Subtype - physiology Infrared imaging systems Laboratory animals Madin Darby Canine Kidney Cells Mammals Mice Mice, Inbred BALB C Mutation Nucleotide sequence Orthomyxoviridae Infections - pathology Orthomyxoviridae Infections - virology Pandemics Pathogenicity pb2 gene pb2-r251k Plasmids polymerase Proteins Public health Replication RNA-Dependent RNA Polymerase - genetics RNA-Dependent RNA Polymerase - metabolism Swine flu Swine influenza Transcription Viral infections Viral Proteins - genetics Viral Proteins - metabolism Virulence Virulence - genetics Virus Replication - genetics Viruses United States > US China pathogenicity PB2 gene Eurasian avian-like H1N1 swine influenza viruses polymerase PB2-R251K
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Summary:	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 TCID 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 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.
ISSN:	1999-4915 1999-4915
DOI:	10.3390/v12010052