DRBP76 associates with Ebola virus VP35 and suppresses viral polymerase function.

DRBP76 associates with Ebola virus VP35 and suppresses viral polymerase function.
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DRBP76 与埃博拉病毒 VP35 结合并抑制病毒聚合酶功能。

DOI:
10.1093/infdis/jir343
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发表时间:
2011
期刊:
The Journal of infectious diseases
影响因子:
--
通讯作者:
Basler,ChristopherF
Basler,ChristopherF
中科院分区:
--
文献类型:
--
作者:
Shabman,ReedS;Leung,DaisyW;Johnson,Joshua;Glennon,Nicole;Gulcicek,ErolE;Stone,KathrynL;Leung,Lawrence;Hensley,Lisa;Amarasinghe,GayaK;Basler,ChristopherF

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扎伊尔埃博拉病毒(EBOV)蛋白VP 35是多功能的;它抑制IFN-α/β的产生,并作为病毒RNA聚合酶的辅因子发挥作用。质谱鉴定了双链RNA结合蛋白76(DRBP 76/NFAR-1/NF 90)作为与VP 35 C-末端干扰素抑制结构域(IID)相关的细胞因子。DRBP 76被描述为调节宿主细胞蛋白质合成,并在宿主防御中发挥重要作用。VP 35-IID-DRBP 76相互作用需要添加外源dsRNA,但在不存在外源dsRNA的情况下全长VP 35与DRBP 76缔合。用表达VP 35的纽卡斯尔病病毒(NDV)感染的细胞将DRBP 76从细胞核重新分配到细胞质,细胞质是EBOV复制的隔室。DRBP 76的过表达没有改变VP 35抑制I型IFN产生的能力,但确实损害了EBOV转录/复制复合物的功能。这些数据表明DRBP 76通过其与VP 35的结合发挥抗EBOV功能。
The Zaire Ebola virus (EBOV) protein VP35 is multifunctional; it inhibits IFN-α/β production and functions as a cofactor of the viral RNA polymerase. Mass spectrometry identified the double stranded RNA binding protein 76 (DRBP76/NFAR-1/NF90) as a cellular factor that associates with the VP35 C-terminal interferon inhibitory domain (IID). DRBP76 is described to regulate host cell protein synthesis and play an important role in host defense. The VP35-IID-DRBP76 interaction required the addition of exogenous dsRNA, but full-length VP35 associated with DRBP76 in the absence of exogenous dsRNA. Cells infected with a Newcastle disease virus (NDV)–expressing VP35 redistributed DRBP76 from the nucleus to the cytoplasm, the compartment in which EBOV replicates. Overexpression of DRBP76 did not alter the ability of VP35 to inhibit type I IFN production but did impair the function of the EBOV transcription/replication complex. These data suggest that DRBP76, via its association with VP35, exerts an anti-EBOV function.
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