Induction of suppressor of cytokine signaling-3 by herpes simplex virus type 1 confers efficient viral replication.
Induction of suppressor of cytokine signaling-3 by herpes simplex virus type 1 confers efficient viral replication.
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DOI：
10.1016/j.virol.2005.04.028
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发表时间：
2005-07
期刊：
影响因子：
3.7
通讯作者：
S. Yokota;N. Yokosawa;T. Okabayashi;T. Suzutani;N. Fujii
中科院分区：
文献类型：
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作者：
S. Yokota;N. Yokosawa;T. Okabayashi;T. Suzutani;N. Fujii
我们以前表明，感染单纯疱疹病毒1型（HSV-1）迅速诱导抑制细胞因子信号传导-3（SOCS 3），一个主机的JAK/STAT途径的负调节，在羊膜细胞系FL。因此，HSV-1抑制干扰素（IFN）信号传导途径在IFN诱导的磷酸化的Janus激酶在感染的早期阶段。在本研究中，我们研究了SOCS 3诱导HSV-1感染的几种类型的人类细胞系。FL细胞和T细胞系CCRF-CEM在HSV-1感染期间强烈诱导SOCS 3。病毒在两种细胞系中快速繁殖并产生裂解性感染。另一方面，单核细胞系U937和THP-1以及B细胞系AKATA在HSV-1感染期间既不显示SOCS 3诱导也不显示IFN诱导的STAT 1磷酸化的抑制。这些细胞系导致持续或延长的感染，其持续产生低滴度的感染性病毒。HSV-1对SOCS 3的诱导应在HSV-1感染后立即通过STAT 3活化发生。通过添加Jak 3抑制剂WHI-P131抑制SOCS 3诱导。用WHI-P131处理或转染对SOCS 3特异的反义寡核苷酸显著抑制HSV-1在FL细胞中的复制。在存在中和性抗IFN-α和抗IFN-β抗体的情况下，WHI-P131对病毒复制的抑制被释放。总之，HSV-1诱导的SOCS 3抑制IFN信号传导是HSV-1有效复制和裂解感染所必需的。SOCS 3诱导在细胞系之间变化，表明它是决定HSV-1有效复制的细胞类型特异性的重要因素。
We showed previously that infection of herpes simplex virus type 1 (HSV-1) rapidly induced the suppressor of cytokine signaling-3 (SOCS3), a host negative regulator of the JAK/STAT pathway, in the amnion cell line FL. Thus, HSV-1 suppresses the interferon (IFN) signaling pathway at the step of IFN-induced phosphorylation of janus kinases during an early infection stage. In the present study, we examined SOCS3 induction by HSV-1 infection in several types of human cell lines. FL cells and the T-cell line CCRF-CEM strongly induced SOCS3 during HSV-1 infection. The virus rapidly propagated in both cell lines and produced a lytic infection. On the other hand, the monocytic cell lines U937 and THP-1, and the B-cell line AKATA showed neither SOCS3 induction nor suppression of IFN-induced STAT1 phosphorylation during HSV-1 infection. These cell lines resulted in a persistent or prolonged infection, which continuously produced a low titer of infectious virus. The induction of SOCS3 by HSV-1 should occur via STAT3 activation immediately after HSV-1 infection. SOCS3 induction was inhibited by the addition of a Jak3 inhibitor WHI-P131. Treatment with WHI-P131 or transfection of antisense oligonucleotides specific for SOCS3 dramatically suppressed replication of HSV-1 in FL cells. The suppression of viral replication by WHI-P131 was released in the presence of neutralizing anti-IFN-α and anti-IFN-β antibodies. In conclusion, suppression of IFN signaling by HSV-1-induced SOCS3 is required for efficient replication and lytic infection of HSV-1. The SOCS3 induction varied among cell lines, indicating that it is an important factor determining the cell type specificity of efficient HSV-1 replication.