|Deletions of MGF110-9L and MGF360-9L from African swine fever virus are highly attenuated in swine and confer protection against homologous challenge|
|Li, Dan; Ren, Jingjing; Zhu, Guoqiang; Wu, Panxue; Yang, Wenping; Ru, Yi; Feng, Tao; Liu, Huanan; Zhang, Jing; Peng, Jiangling; Tian, Hong; Liu, Xiangtao; Zheng, Haixue|
|Online publication date||2023-05
|Source Publication||JOURNAL OF BIOLOGICAL CHEMISTRY
Impact Factor & Quartile|
|Abstract||African swine fever, caused by a large icosahedral DNA virus (African swine fever virus, ASFV), is a highly contagious disease in domestic and feral swine, thus posing a significant economic threat to the global swine industry. Currently, there are no effective vaccines or the available methods to control ASFV infection. Attenuated live viruses with deleted virulence factors are considered to be the most promising vaccine candidates; however, the mechanism by which these attenuated viruses confer protection is unclear. Here, we used the Chinese ASFV CN/GS/2018 as a backbone and used homologous recombination to generate a virus in which MGF110-9L and MGF360-9L, two genes antagonize host innate antiviral immune response, were deleted (ASFV-ΔMGF110/360-9L). This genetically modified virus was highly attenuated in pigs and provided effective protection of pigs against parental ASFV challenge. Importantly, we found ASFV-ΔMGF110/360-9L infection induced higher expression of Toll-like receptor 2 (TLR2) mRNA compared with parental ASFV as determined by RNA-Seq and RT-PCR analysis. Further immunoblotting results showed that parental ASFV and ASFV-ΔMGF110/360-9L infection inhibited Pam3CSK4-triggered activating phosphorylation of proinflammatory transcription factor NF-κB subunit p65 and phosphorylation of NF-κB inhibitor IκBα levels, although NF-κB activation was higher in ASFV-ΔMGF110/360-9L-infected cells compared with parental ASFV-infected cells. Additionally, we show overexpression of TLR2 inhibited ASFV replication and the expression of ASFV p72 protein, whereas knockdown of TLR2 had the opposite effect. Our findings suggest that the attenuated virulence of ASFV-ΔMGF110/360-9L might be mediated by increased NF-κB and TLR2 signaling. © 2023 The Authors|
Polymerase chain reaction
African swine fever virus
Toll-like receptor 2
|Publisher||American Society for Biochemistry and Molecular Biology Inc.
|WOS Research Area||Biochemistry & Molecular Biology
|WOS Subject||Biochemistry & Molecular Biology
|EI Accession Number||20232214154053
|EI Classification Number||461.2 Biological Materials and Tissue Engineering
; 461.6 Medicine and Pharmacology
; 461.9 Biology
; 801.2 Biochemistry
; 802.2 Chemical Reactions
; 804 Chemical Products Generally
|Original Document Type||Journal article (JA)
|Corresponding Author||Zheng, Haixue|
State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, China
|First Author Affilication||Lanzhou University
|Corresponding Author Affilication||Lanzhou University
Li, Dan,Ren, Jingjing,Zhu, Guoqiang,et al. Deletions of MGF110-9L and MGF360-9L from African swine fever virus are highly attenuated in swine and confer protection against homologous challenge[J].
JOURNAL OF BIOLOGICAL CHEMISTRY,2023,299(6).
Li, Dan.,Ren, Jingjing.,Zhu, Guoqiang.,Wu, Panxue.,Yang, Wenping.,...&Zheng, Haixue.(2023).Deletions of MGF110-9L and MGF360-9L from African swine fever virus are highly attenuated in swine and confer protection against homologous challenge.JOURNAL OF BIOLOGICAL CHEMISTRY,299(6).
Li, Dan,et al."Deletions of MGF110-9L and MGF360-9L from African swine fever virus are highly attenuated in swine and confer protection against homologous challenge".JOURNAL OF BIOLOGICAL CHEMISTRY 299.6(2023).
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