Human T Cell Leukemia Virus Type 1 Tax Inhibits Innate Antiviral Signaling via NF-κB-Dependent Induction of SOCS1
Human T Cell Leukemia Virus Type 1 Tax Inhibits Innate Antiviral Signaling via NF-κB-Dependent Induction of SOCS1
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DOI：
10.1128/jvi.00007-11
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发表时间：
2011-07-01
影响因子：
5.4
通讯作者：
Harhaj, Edward W.
中科院分区：
文献类型：
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作者：
Charoenthongtrakul, Soratree;Zhou, Qinjie;Harhaj, Edward W.
人类T细胞白血病病毒1型（HTLV-1）抑制宿主抗病毒信号通路，但其潜在机制尚不清楚。在这里，我们发现HTLV-1 Tax癌蛋白诱导SOCS 1的表达，SOCS 1是干扰素信号传导的抑制剂。Tax需要NF-κ B而不是CREB来诱导T细胞中SOCS 1的表达。此外，Tax在转染细胞和HTLV-1转化细胞系中与SOCS 1相互作用。虽然SOCS 1通常是一种短寿命蛋白，但在Tax的存在下，SOCS 1的稳定性大大增加。因此，Tax以SOCS 1依赖的方式增强了异源病毒水泡性口炎病毒（VSV）的复制。令人惊讶的是，Tax需要SOCS 1来抑制RIG-I依赖的抗病毒信号传导，而不是干扰素诱导的JAK/STAT途径。在HTLV-1转化的细胞系MT-2中，通过RNA介导的干扰抑制SOCS 1导致IFN-β表达增加，同时HTLV-1复制和p19（Gag）水平降低。综上所述，我们的研究结果表明，Tax抑制抗病毒信号，部分是通过劫持干扰素调节蛋白。
Human T cell leukemia virus type 1 (HTLV-1) inhibits host antiviral signaling pathways although the underlying mechanisms are unclear. Here we found that the HTLV-1 Tax oncoprotein induced the expression of SOCS1, an inhibitor of interferon signaling. Tax required NF-kappa B, but not CREB, to induce the expression of SOCS1 in T cells. Furthermore, Tax interacted with SOCS1 in both transfected cells and in HTLV-1-transformed cell lines. Although SOCS1 is normally a short-lived protein, in the presence of Tax, the stability of SOCS1 was greatly increased. Accordingly, Tax enhanced the replication of a heterologous virus, vesicular stomatitis virus (VSV), in a SOCS1-dependent manner. Surprisingly, Tax required SOCS1 to inhibit RIG-Idependent antiviral signaling, but not the interferon-induced JAK/STAT pathway. Inhibition of SOCS1 by RNA-mediated interference in the HTLV-1-transformed cell line MT-2 resulted in increased IFN-beta expression accompanied by reduced HTLV-1 replication and p19(Gag) levels. Taken together, our results reveal that Tax inhibits antiviral signaling, in part, by hijacking an interferon regulatory protein.