1. African swine fever virus pH240R enhances viral replication via inhibition of the type I IFN signaling pathway.
- Author
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Guangqiang Ye, Zhaoxia Zhang, Xiaohong Liu, Hongyang Liu, Weiye Chen, Chunying Feng, Jiangnan Li, Qiongqiong Zhou, Dongming Zhao, Shuai Zhang, Hefeng Chen, Zhigao Bu, Li Huang, and Changjiang Weng
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AFRICAN swine fever virus , *CLASSICAL swine fever , *VIRAL replication , *JAK-STAT pathway , *CELLULAR signal transduction , *AFRICAN swine fever , *TYPE I interferons - Abstract
African swine fever (ASF) is an acute, hemorrhagic, and severe infectious disease caused by ASF virus (ASFV) infection. At present, there are still no safe and effective drugs and vaccines to prevent ASF. Mining the important proteins encoded by ASFV that affect the virulence and replication of ASFV is the key to developing effective vaccines and drugs. In this study, ASFV pH240R, a capsid protein of ASFV, was found to inhibit the type I interferon (IFN) signaling pathway. Mechanistically, pH240R interacted with IFNAR1 and IFNAR2 to disrupt the interaction of IFNAR1-TYK2 and IFNAR2-JAK1. Additionally, pH240R inhibited the phosphorylation of IFNAR1, TYK2, and JAK1 induced by IFN-a, resulting in the suppression of the nuclear import of STAT1 and STAT2 and the expression of IFN-stimulated genes (ISGs). Consistent with these results, H240R-deficient ASFV (ASFV-ΔH240R) infection induced more ISGs in porcine alveolar macrophages compared with its parental ASFV HLJ/18. We also found that pH240R enhanced viral replication via inhibition of ISGs expression. Taken together, our results clarify that pH240R enhances ASFV replication by inhibiting the JAK-STAT signaling pathway, which highlights the possibility of pH240R as a potential drug target. [ABSTRACT FROM AUTHOR]
- Published
- 2024
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