How to Inhibit Nuclear Factor-Kappa B Signaling: Lessons from Poxviruses.

How to Inhibit Nuclear Factor-Kappa B Signaling: Lessons from Poxviruses.
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DOI:
10.3390/pathogens11091061
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发表时间:
2022-09-18
期刊:
Pathogens (Basel, Switzerland)
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其他
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核因子-κ B(NF-κB)家族的转录因子调节关键的宿主炎症和抗病毒基因表达程序,因此,通常在病毒感染期间通过模式识别受体和病毒碱-受体相互作用的作用被激活。反过来,许多病毒病原体编码操纵和/或抑制NF-κB信号传导的策略。这特别由编码NF-κB信号传导的至少18种不同抑制剂的原型痘病毒痘苗病毒(VV)例示。虽然这些痘病毒NF-κB抑制剂中的许多对于细胞培养物中的VV复制不是必需的,但它们实际上都调节动物模型中的VV毒力,强调了痘病毒-NF-κB途径相互作用对病毒发病机制的重要影响。本文综述VV编码的拮抗剂抑制NF-κB通路初始活化和NF-κB信号中间体的机制,以及NF-κB转录因子复合物的活化和功能。
The Nuclear Factor-kappa B (NF-κB) family of transcription factors regulates key host inflammatory and antiviral gene expression programs, and thus, is often activated during viral infection through the action of pattern-recognition receptors and cytokine–receptor interactions. In turn, many viral pathogens encode strategies to manipulate and/or inhibit NF-κB signaling. This is particularly exemplified by vaccinia virus (VV), the prototypic poxvirus, which encodes at least 18 different inhibitors of NF-κB signaling. While many of these poxviral NF-κB inhibitors are not required for VV replication in cell culture, they virtually all modulate VV virulence in animal models, underscoring the important influence of poxvirus–NF-κB pathway interactions on viral pathogenesis. Here, we review the diversity of mechanisms through which VV-encoded antagonists inhibit initial NF-κB pathway activation and NF-κB signaling intermediates, as well as the activation and function of NF-κB transcription factor complexes.
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