RNA-binding protein isoforms ZAP-S and ZAP-L have distinct antiviral and immune resolution functions.,Nature Immunology

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RNA-binding protein isoforms ZAP-S and ZAP-L have distinct antiviral and immune resolution functions.
Nature Immunology ( IF 27.7 ) Pub Date : 2019-11-18 , DOI: 10.1038/s41590-019-0527-6
Johannes Schwerk ₁ , Frank W Soveg ₁ , Andrew P Ryan ₂ , Kerri R Thomas ₁ , Lauren D Hatfield ₁ , Snehal Ozarkar ₁ , Adriana Forero ₁ , Alison M Kell ₁ , Justin A Roby ₁ , Lomon So _{1,

3} , Jennifer L Hyde ₄ , Michael Gale _{1,

5} , Matthew D Daugherty ₂ , Ram Savan _{1,

5}

Affiliation

The initial response to viral infection is anticipatory, with host antiviral restriction factors and pathogen sensors constantly surveying the cell to rapidly mount an antiviral response through the synthesis and downstream activity of interferons. After pathogen clearance, the host's ability to resolve this antiviral response and return to homeostasis is critical. Here, we found that isoforms of the RNA-binding protein ZAP functioned as both a direct antiviral restriction factor and an interferon-resolution factor. The short isoform of ZAP bound to and mediated the degradation of several host interferon messenger RNAs, and thus acted as a negative feedback regulator of the interferon response. In contrast, the long isoform of ZAP had antiviral functions and did not regulate interferon. The two isoforms contained identical RNA-targeting domains, but differences in their intracellular localization modulated specificity for host versus viral RNA, which resulted in disparate effects on viral replication during the innate immune response.

中文翻译：

RNA 结合蛋白异构体 ZAP-S 和 ZAP-L 具有不同的抗病毒和免疫解决功能。

对病毒感染的最初反应是预期性的，宿主抗病毒限制因子和病原体传感器不断地检测细胞，通过干扰素的合成和下游活性迅速产生抗病毒反应。清除病原体后，宿主解决这种抗病毒反应并恢复体内平衡的能力至关重要。在这里，我们发现 RNA 结合蛋白 ZAP 的同种型既可以作为直接的抗病毒限制因子，也可以作为干扰素分解因子。ZAP 的短亚型与几种宿主干扰素信使 RNA 结合并介导其降解，因此充当干扰素反应的负反馈调节剂。相比之下，ZAP 的长异构体具有抗病毒功能并且不调节干扰素。

更新日期：2019-11-18

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