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Abstract

African swine fever virus (ASFV) causes feverous and hemorrhagic disease of domestic pigs and European wild boars with high mortality, yet no commercial vaccine is currently available. Several ASFV strains with natural deletion or gene-targeted knockout of multiple MGF360 and MGF505 genes are attenuated in vitro and in vivo, and can offer full protection against homologous challenge. However, the mechanisms underlying the protection are not fully understood. This study aims to investigate the effects of MGF360-12L of ASFV-SY18 on the cGAS-STING signaling pathway and explore the potential mechanisms. We identified that ASFV-SY18 MGF360-12L could inhibit cGAS-STING, TBK1, or IRF3-5D-stimulated IFN-β expression and ISRE activation. Specifically, MGF360-12L inhibits both the activation of PRD(III-I) in a dose-dependent manner, and suppresses the exogenous expression of TBK1 and IRF3-5D. MGF360-12L could block NF-κB activation induced by overexpression of cGAS-STING, TBK1, IKKβ. Downstream of the IFN-β signaling, MGF360-12L blocks the ISRE promoter activation by reducing total protein level of IRF9. Moreover, MGF360-12L protein can inhibit IFN-β-mediated antiviral effects. In conclusion, our findings suggest that MGF360-12L is a multifunctional immune-evasion protein that inhibits both the expression and effect of IFN-β, which could partially explain the attenuation of relevant gene-deleted ASFV strains, and shed light on the development of efficient ASFV live attenuated vaccines in the future.
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Authors and Affiliations

Q. Chen
1
X.X. Wang
2
S.W. Jiang
1
X.T. Gao
3
S.Y. Huang
1
Y. Liang
1
H. Jia
2
H.F. Zhu
2

  1. Key Laboratory of Northern Urban Agriculture of Ministry of Agriculture and Rural Affairs, College of Bioscience and Resource Environment, Beijing University of Agriculture, No. 7 Beinong Road, Changping District, 102206 Beijing, China
  2. Department of Veterinary Medicine, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences, No. 2 Yuanmingyuan West Road, Haidian District, 100193 Beijing, China
  3. Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, No. 12 Zhongguancun South Street, Haidian District, 100081 Beijing, China
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Abstract

Porcine contagious pleuropneumonia (PCP) is a very serious respiratory disease which is difficult to prevent and treat. In this study, the therapeutic effects of lithium chloride (LiCl) on PCP were examined using a mouse model. A mouse model of PCP was established by intranasal infections with Actinobacillus pleuropneumoniae (App). Histopathological analysis was performed by routine paraffin sections and an H-E staining method. The inflammatory factors, TLR4 and CCL2 were analyzed by qPCR. The expression levels of p-p65 and pGSK-3ß were detected using the Western Blot Method. The death rates, clinical symptoms, lung injuries, and levels of TLR-4, IL-1ß, IL-6, TNF-α, and CCL2 were observed to decrease in the App-infected mice treated with LiCl. It was determined that the LiCl treatments had significantly reduced the mortality of the App-infected cells, as well as the expressions of p-p65 and pGSK-3ß. The results of this study indicated that LiCl could improve the pulmonary injuries of mice caused by App via the inhibition of the GSK-3β-NF-κB-dependent pathways, and may potentially become an effective drug for improving pulmonary injuries caused by PCP.
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Authors and Affiliations

Y. Zhang
1
W. Xu
1
Y. Tang
1
F. Huang
1 2

  1. College of Veterinary Medicine, Hunan Agricultural University, Furong District, Nongda Road, No.1, Changsha 410128, China
  2. Hunan Engineering Technology Research Center for Veterinary Drugs, Hunan Agricultural University, Furong District, Nongda Road, No.1, Changsha 410128, China

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