猪繁殖与呼吸综合征病毒
生物
趋化因子
转录因子
分子生物学
干扰素
干扰素调节因子
报告基因
特里夫
细胞生物学
Toll样受体
病毒学
免疫学
病毒
先天免疫系统
基因
炎症
基因表达
免疫系统
生物化学
作者
Yanwei Wang,Rui Luo,Liurong Fang,Dan Wang,Jing Bi,Huanchun Chen,Shaobo Xiao
标识
DOI:10.1016/j.molimm.2010.10.022
摘要
RANTES (regulated upon activation, normally T-cell expressed and presumably secreted), a CC chemokine, plays an important role in the inflammatory response associated with viral infections. Previous studies have demonstrated that infection with porcine reproductive and respiratory syndrome virus (PRRSV) induces RANTES transcription in vitro and in vivo. However, the molecular mechanism remains unclear. In this study, real-time RT-PCR and promoter luciferase reporter assays showed that PRRSV infection significantly upregulates RANTES gene transcription in both a time- and dose-dependent manner and this induction requires viral replication in MARC-145 cells. Promoter mutagenesis experiments found that the nuclear factor (NF-κB) binding sites play an important role in PRRSV-induced RANTES transcription, while the interferon-stimulated responsive element (ISRE) site is not essential. PRRSV-induced RANTES transcription was dramatically inhibited by administration of a dominant-negative mutant of IκB kinase alpha (mIκBα), NF-κB inhibitor BAY11-7082 or ERK1/2 inhibitor U0126. In addition, the use of dominant-negative mutants of various adaptor molecules of the Toll-like receptor (TLR) or RIG-I-like receptor (RLR) signaling pathways demonstrated that PRRSV upregulated RANTES transcription is dependent on myeloid differentiation primary response gene 88 (MyD88), TIR domain-containing adaptor inducing IFN-β (TRIF) and TNF receptor-associated factor 6 (TRAF6), indicating that the TLR signaling pathway is involved in PRRSV-induced RANTES activation.
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