首页|Porcine TRIM35 positively regulate TRAF3-mediated IFN-beta production and inhibit Japanese encephalitis virus replication
Porcine TRIM35 positively regulate TRAF3-mediated IFN-beta production and inhibit Japanese encephalitis virus replication
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NSTL
Elsevier
Tripartite motif 35 (TRIM35) protein is a ubiquitin E3 ligase that mediates interferon-beta (IFN-beta) production via regulating ubiquitination of multiple adaptor proteins in innate immune signaling pathways. Here, we cloned the porcine TRIM35 (porTRIM35) gene and analyzed its involvement in IFN-beta expression as well as the antiviral response against Japanese encephalitis virus (JEV). The full-length porTRIM35 gene encoded a 493-amino acid protein and exhibited 79.6%-89.5% sequence similarity with its orthologues in humans, mice, monkeys and rabbits. porTRIM35 possessed typical structural features of TRIMs, including a RING domain, a B-box domain, a coiled-coil domain and a PRY/SPYR domain. Exogenous overexpression of porTRIM35 significantly up-regulated the mRNA expression level of IFN-beta in swine testicular (ST) cell in response to poly(I:C) stimulation, whereas knockdown endogenous expression of porTRIM35 lead to a decrease in the expression level of IFN-beta. Mechanically, porTRIM35 directly interacted with porcine TNF-receptor associated factor 3 (TRAF3) and catalyzed its Lys63-linked polyubiquitination, thereby leading to the up-regulation of IFN-beta production. Meanwhile, we demonstrated that the RING and PRY/SPRY domains were essential for the E3 ligase activity of porTRIM35. In response to JEV infection, the endogenous expression of porTRIM35 was markedly inhibited at the mRNA level, while exogenous expression of porTRIM35 significantly elevated the expression of IFN-beta induced by JEV infection and reduced viral titers in ST cells, suggesting that porTRIM35 is a negative regulator for JEV replication. These data demonstrate the importance of porTRIM35 in IFN-beta expression as well as the antiviral response against JEV replication.
NSTL
Elsevier
