Human metapneumovirus small hydrophobic (SH) protein downregulates type I IFN pathway signaling by affecting STAT1 expression and phosphorylation.
Human metapneumovirus small hydrophobic (SH) protein downregulates type I IFN pathway signaling by affecting STAT1 expression and phosphorylation.
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DOI：
10.1016/j.virol.2016.04.022
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发表时间：
2016-07
期刊：
影响因子：
3.7
通讯作者：
Williams JV
中科院分区：
文献类型：
--
作者：
Hastings AK;Amato KR;Wen SC;Peterson LS;Williams JV
I型干扰素是抗病毒免疫的重要介体。人类偏肺病毒(HMPV)抑制干扰素信号转导，但不编码已知的干扰素拮抗剂的同源物。我们验证了一种假设，即特定的病毒蛋白通过靶向信号转导和转录激活因子-1(STAT1)来阻止I型干扰素信号转导。我们发现，由于固有的负反馈，即使在没有直接感染的情况下，人类呼吸道上皮细胞(能够表达IFN)的STAT1磷酸化也受到了损害。与模型感染细胞相比，hMPV感染的Vero细胞(不能表达干扰素)在I型干扰素治疗后表现出较低的STAT1表达和受损的STAT1磷酸化。瞬时过表达HMPV小分子疏水蛋白(SH)显著抑制STAT1的磷酸化和信号转导，而缺失SH蛋白的重组病毒不能抑制STAT1的磷酸化。我们的结果表明，HMPV的SH蛋白通过靶向STAT1而下调I型干扰素信号。
Type I interferon (IFN) is a key mediator of antiviral immunity. Human metapneumovirus (HMPV) inhibits IFN signaling, but does not encode homologues of known IFN antagonists. We tested the hypothesis that a specific viral protein prevents type I IFN signaling by targeting signal transducer and activator of transcription-1 (STAT1). We found that human airway epithelial cells (capable of expressing IFNs) became impaired for STAT1 phosphorylation even without direct infection due to intrinsic negative feedback. HMPV-infected Vero cells (incapable of expressing IFN) displayed lower STAT1 expression and impaired STAT1 phosphorylation in response to type I IFN treatment compared to mock-infected cells. Transient overexpression of HMPV small hydrophobic (SH) protein significantly inhibited STAT1 phosphorylation and signaling, and recombinant virus lacking SH protein was unable to inhibit STAT1 phosphorylation. Our results indicate a role for the SH protein of HMPV in the downregulation of type I IFN signaling through the targeting of STAT1.