ARHGEF18 can promote BVDV NS5B activation of the host NF-κB signaling pathway by combining with the NS5B-palm domain

• Published in: Veterinary microbiology 2024-04, Vol.291, p.109911-109911, Article 109911
• Main Authors: Yin, Jiying, Diao, Naichao, Tian, Tian, Wang, Qi, Ma, Shuqi, He, Ning, Zhou, Hongming, Zhou, Zehui, Jia, Wenyi, Wang, Xiaonan, Shi, Kun, Du, Rui
• Format: Article
• Language: English
• Subjects: ARHGEF18; Bovine viral diarrhea virus; NF-κB; NS5B-palm
• ISSN: 0378-1135; 1873-2542
• DOI: 10.1016/j.vetmic.2023.109911

Rho guanine nucleotide exchange factor 18 (ARHGEF18) is a member of the Rho guanine nucleotide exchange factor (RhoGEF) family. RhoGEF plays an important role in the occurrence of tumors and neurological diseases; however, its involvement in host cell resistance against pathogenic microorganisms is mostly unknown. Herein, we report that bovine viral diarrhea virus (BVDV) nonstructural protein 5B (NS5B) can activate the nuclear factor kappa B (NF-κB) signaling pathway to induce an immune response. To clarify the functional domains of NS5B that activate NF-κB signaling, the six structural domains of NS5B were expressed separately: NS5B-core, NS5B-finger, NS5B-palm, NS5B-thumb, NS5B-N and NS5B-c domain. We preliminarily determined that the functional domains of NS5B that activate NF-κB signaling are the finger and palm domains. We used a bovine kidney cell cDNA library and yeast two-hybrid technology to identify that the host protein ARHGEF18 interacts with NS5B. Co-immunoprecipitation assays showed that ARHGEF18 interacts strongly with NS5B-palm. Interestingly ARHGEF18 could promote NF-κB signaling activation by BVDV NS5B. In addition silencing ARHGEF18 significantly inhibited NS5B-palm activation of NF-κB signaling. We concluded that ARHGEF18 can bind to BVDV NS5B through the palm domain to activate the NF-κB pathway. These findings provide direct evidence that BVDV NS5B induces immune responses by activating NF-κB signaling. •We investigated the activation of NF-κB by bovine viral diarrhea virus NS5B.•Truncation analysis indicated that NS5B-finger and NS5B-palm domains activate NF-κB.•Yeast two-hybrid screening indicated that host ARHGEF18 combines with NS5B-palm.•Silencing of ARHGEF18 inhibited NS5B-mediated activation of NF-κB signaling.•ARHGEF18 combined with NS5B-palm activates the NF-κB signaling pathway.