The cytoplasmic location of chicken mx is not the determining factor for its lack of antiviral activity.
The cytoplasmic location of chicken mx is not the determining factor for its lack of antiviral activity.
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DOI：
10.1371/journal.pone.0012151
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发表时间：
2010-08-16
期刊：
影响因子：
3.7
通讯作者：
Tiley LS
中科院分区：
文献类型：
--
作者：
Benfield CT;Lyall JW;Tiley LS
鸡Mx属于干扰素诱导的动力蛋白样GTP酶的Mx家族，其在某些物种中具有有效的抗病毒特性。存在鸡Mx的抗病毒能力的验证数据。编码Asn 631多态性的等位基因的抗流感活性的报告未得到后续研究的支持。鸡Mx的正常胞质定位可能影响其抗病毒能力。在这里，我们报告了进一步的研究，以确定抗纽卡斯尔病病毒（NDV），一种经济上重要的细胞质RNA病毒的鸡，和Thogoto病毒，正粘病毒是非常敏感的细胞质MxA蛋白从人类的抗病毒潜力的鸡Mx。我们还报告的后果重新定位鸡Mx的核。在病毒感染测定中使用NDV测试鸡Mx。无论是Asn 631还是Ser 631 Mx等位基因（当转染到293 T细胞中时），当细胞随后感染NDV时，都没有显示出对病毒指导的基因表达的抑制。然而，人MxA确实显示出对NDV指导的基因表达的显著抑制。鸡Mx未能抑制Thogoto病毒（THOV）微型复制子系统，其中细胞质人MxA蛋白显示出有效和特异性抑制。通过在鸡Mx的N-末端插入猴病毒40大T抗原核定位序列（SV 40 NLS），实现鸡Mx向核的重新定位。在细胞培养物中病毒感染期间，核重定位的鸡Mx不抑制流感（A/PR/8/34）基因表达，也不抑制A/PR/8/34或A/Turkey/50-92/91微复制子系统中的流感聚合酶活性。鸡Mx蛋白（Asn 631）缺乏对THOV和NDV的抑制作用，并且当人工重新定位于细胞核时不能抑制流感复制。因此，鸡Mx蛋白的天然细胞质定位不能解释其缺乏抗病毒活性。
Chicken Mx belongs to the Mx family of interferon-induced dynamin-like GTPases, which in some species possess potent antiviral properties. Conflicting data exist for the antiviral capability of chicken Mx. Reports of anti-influenza activity of alleles encoding an Asn631 polymorphism have not been supported by subsequent studies. The normal cytoplasmic localisation of chicken Mx may influence its antiviral capacity. Here we report further studies to determine the antiviral potential of chicken Mx against Newcastle disease virus (NDV), an economically important cytoplasmic RNA virus of chickens, and Thogoto virus, an orthomyxovirus known to be exquisitely sensitive to the cytoplasmic MxA protein from humans. We also report the consequences of re-locating chicken Mx to the nucleus. Chicken Mx was tested in virus infection assays using NDV. Neither the Asn631 nor Ser631 Mx alleles (when transfected into 293T cells) showed inhibition of virus-directed gene expression when the cells were subsequently infected with NDV. Human MxA however did show significant inhibition of NDV-directed gene expression. Chicken Mx failed to inhibit a Thogoto virus (THOV) minireplicon system in which the cytoplasmic human MxA protein showed potent and specific inhibition. Relocalisation of chicken Mx to the nucleus was achieved by inserting the Simian Virus 40 large T antigen nuclear localisation sequence (SV40 NLS) at the N-terminus of chicken Mx. Nuclear re-localised chicken Mx did not inhibit influenza (A/PR/8/34) gene expression during virus infection in cell culture or influenza polymerase activity in A/PR/8/34 or A/Turkey/50-92/91 minireplicon systems. The chicken Mx protein (Asn631) lacks inhibitory effects against THOV and NDV, and is unable to suppress influenza replication when artificially re-localised to the cell nucleus. Thus, the natural cytoplasmic localisation of the chicken Mx protein does not account for its lack of antiviral activity.
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DOI：
10.1073/pnas.0403167101
发表时间：
2004-06-15
影响因子：
11.1
作者：
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通讯作者：
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影响因子：
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影响因子：
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