Ebolavirus VP24 Binding to Karyopherins Is Required for Inhibition of Interferon Signaling
Ebolavirus VP24 Binding to Karyopherins Is Required for Inhibition of Interferon Signaling
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DOI：
10.1128/jvi.01372-09
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发表时间：
2010-01-15
影响因子：
5.4
通讯作者：
Volchkov, Viktor E.
中科院分区：
文献类型：
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作者：
Mateo, Mathieu;Reid, St. Patrick;Volchkov, Viktor E.
埃博拉病毒VP 24蛋白通过阻断酪氨酸磷酸化STAT 1（PY-STAT 1）的核积累来抵消α/β干扰素（IFN-α/β）和IFN-γ信号传导。根据提出的模型，VP 24与核粒转运蛋白α（KPN α）核定位信号受体NPI-1亚家族成员的结合会阻止它们与PY-STAT 1结合，从而阻止PY-STAT 1核积聚。这项研究现在确定了抑制IFN-β诱导的基因表达和PY-STAT 1核积累所需的VP 24的两个结构域。我们证明了功能丧失与KPN α蛋白结合丧失相关。因此，VP 24 IFN拮抗剂功能需要VP 24与KPN α相互作用的能力。
The Ebolavirus VP24 protein counteracts alpha/beta interferon (IFN-alpha/beta) and IFN-gamma signaling by blocking the nuclear accumulation of tyrosine-phosphorylated STAT1 (PY-STAT1). According to the proposed model, VP24 binding to members of the NPI-1 subfamily of karyopherin alpha (KPN alpha) nuclear localization signal receptors prevents their binding to PY-STAT1, thereby preventing PY-STAT1 nuclear accumulation. This study now identifies two domains of VP24 required for inhibition of IFN-beta-induced gene expression and PY-STAT1 nuclear accumulation. We demonstrate that loss of function correlates with loss of binding to KPN alpha proteins. Thus, the VP24 IFN antagonist function requires the ability of VP24 to interact with KPN alpha.