Induction of suppressor of cytokine signaling-3 by herpes simplex virus type 1 contributes to inhibition of the interferon signaling pathway
Induction of suppressor of cytokine signaling-3 by herpes simplex virus type 1 contributes to inhibition of the interferon signaling pathway
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DOI：
10.1128/jvi.78.12.6282-6286.2004
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发表时间：
2004-06-01
影响因子：
5.4
通讯作者：
Fujii, N
中科院分区：
文献类型：
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作者：
Yokota, S;Yokosawa, N;Fujii, N
我们以前表明，单纯疱疹病毒1型（HSV-1）抑制干扰素（IFN）信号通路在感染早期阶段在人羊膜细胞系FL。HSV-1抑制IFN诱导的磷酸化Janus激酶（JAK）在感染的FL细胞。在本研究中，我们发现，抑制细胞因子信号传导-3（SOCS3），一个主机的JAK/STAT途径的负调节，是快速诱导HSV-1感染后的FL细胞。在感染后约1至2小时检测到SOCS3蛋白的最大水平。这与HSV-1介导的IFN诱导的JAK磷酸化抑制的发生一致。HSV-1野生型菌株VR3比UL41或UL13缺陷型和对IFN高反应的突变体更有效地诱导SOCS3。以JAK/STAT途径依赖性方式发生的IRF-7蛋白的诱导和IFN-α 4的转录激活被VR3不良地诱导，但被突变病毒有效地诱导。与此相反，IPX-3的磷酸化和IFN-β的转录激活，这是JAK/STAT途径独立的过程，同样很好地诱导野生型菌株和突变体。总之，SOCS3蛋白似乎是主要负责抑制IFN信号和IFN的生产，发生在HSV-1感染。
We showed previously that herpes simplex virus type 1 (HSV-1) suppresses the interferon (IFN) signaling pathway during the early infection stage in the human amnion cell line FL. HSV-1 inhibits the IFN-induced phosphorylation of Janus kinases (JAK) in infected FL cells. In the present study, we showed that the suppressor of cytokine signaling-3 (SOCS3), a host negative regulator of the JAK/STAT pathway, is rapidly induced in FL cells after HSV-1 infection. Maximal levels of SOCS3 protein were detected at around 1 to 2 h after infection. This is consistent with the occurrence of HSV-1-mediated inhibition of IFN-induced JAK phosphorylation. The HSV-1 wild-type strain VR3 induced SOCS3 more efficiently than did mutants that are defective in UL41 or UL13 and that are hyperresponsive to IFN. Induction of the IRF-7 protein and transcriptional activation of IFN-alpha4, which occur in a JAK/STAT pathway-dependent manner, were poorly induced by VR3 but efficiently induced by the mutant viruses. In contrast, phosphorylation of IPX-3 and transcriptional activation of IFN-beta, which are JAK/STAT pathway-independent process, were equally well induced by the wild-type strain and the mutants. In conclusion, the SOCS3 protein appears to be mainly responsible for the suppression of IFN signaling and IFN production that occurs during HSV-1 infection.