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尼帕病毒样颗粒的蛋白质组组成。

Proteomic composition of Nipah virus-like particles.

机构信息

Department of Biochemistry and Molecular Biology, ERI BioTecMed, University of Valencia, Dr. Moliner 50, 46100 Burjassot, Spain.

Department of Biochemistry and Molecular Biology, ERI BioTecMed, University of Valencia, Dr. Moliner 50, 46100 Burjassot, Spain.

出版信息

J Proteomics. 2018 Feb 10;172:190-200. doi: 10.1016/j.jprot.2017.10.012. Epub 2017 Oct 29.

Abstract

UNLABELLED

Virions are often described as virus-only entities with no cellular components with the exception of the lipids in their membranes. However, advances in proteomics are revealing substantial amounts of host proteins in the viral particles. In the case of Nipah virus (NiV), the viral components in the virion have been known for some time. Nonetheless, no information has been obtained regarding the cellular proteins in the viral particles. To address this question, we produced Virus-Like Particles (VLPs) for NiV by expressing the F, G and M proteins in human-derived cells. Next, the proteomic content in these VLPs was analyzed by LC-MS/MS. We identified 67 human proteins including soluble and membrane-bound proteins involved in vesicle sorting and transport. Interestingly, many of them have been reported to interact with other viruses. Finally, thanks to the semi-quantitative nature of our data we were able to estimate the ratio among F, G and M proteins and also the ratio between cellular and viral proteins in the VLPs. We believe our data contribute to the better understanding of NiV life cycle and might facilitate future attempts for developing antiviral agents and the design of further experimental studies for this deadly infection.

BIOLOGICAL SIGNIFICANCE

Traditionally viral particles have been described as pure entities carrying only viral-derived proteins. Advances in proteomics are changing this simplified view. Host proteins have been identified in many viruses (especially in enveloped viruses). These cell-derived proteins participate in multiple steps in the viral life cycle and might be as important for the survival of the virus as any other viral-encoded protein. In this work, we analyze utilizing LC-MS/MS the cellular proteins incorporated or bound to the virions of Nipah virus (NiV), an emerging, highly pathogenic, zoonotic virus from the Paramyxoviridiae family. Furthermore, we analyzed the ratio between cellular and viral proteins and among the viral F, G and M proteins in the viral particles. The characterization of the Nipah virus-human interactions occurring in the virion might facilitate the development of new therapeutic and prophylactic therapies for this viral illness.

摘要

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病毒粒子通常被描述为仅含有病毒成分的实体,除了它们膜中的脂质外,没有任何细胞成分。然而,蛋白质组学的进步正在揭示大量宿主蛋白存在于病毒粒子中。在尼帕病毒(NiV)的情况下,一段时间以来,人们已经知道病毒粒子中的病毒成分。尽管如此,关于病毒粒子中的细胞蛋白还没有得到任何信息。为了解决这个问题,我们通过在人源细胞中表达 F、G 和 M 蛋白来生产 NiV 的病毒样颗粒(VLPs)。接下来,通过 LC-MS/MS 分析这些 VLPs 中的蛋白质组内容。我们鉴定了 67 种人类蛋白,包括参与囊泡分拣和运输的可溶性和膜结合蛋白。有趣的是,其中许多蛋白已被报道与其他病毒相互作用。最后,由于我们数据的半定量性质,我们能够估计 F、G 和 M 蛋白之间的比例,以及 VLPs 中细胞蛋白和病毒蛋白之间的比例。我们相信我们的数据有助于更好地理解 NiV 的生命周期,并可能为未来开发抗病毒药物和进一步设计针对这种致命感染的实验研究提供便利。

生物学意义

传统上,病毒粒子被描述为仅携带病毒衍生蛋白的纯实体。蛋白质组学的进步正在改变这种简化的观点。已经在许多病毒(尤其是包膜病毒)中鉴定出宿主蛋白。这些源自细胞的蛋白参与病毒生命周期的多个步骤,并且与任何其他病毒编码蛋白一样,对病毒的存活可能同样重要。在这项工作中,我们利用 LC-MS/MS 分析了尼帕病毒(NiV)病毒粒子中包含或结合的细胞蛋白,NiV 是一种新兴的、高致病性、人畜共患的副粘病毒科病毒。此外,我们分析了病毒粒子中细胞蛋白和病毒蛋白之间以及病毒 F、G 和 M 蛋白之间的比例。对发生在病毒粒子中的尼帕病毒-人类相互作用的表征可能有助于为这种病毒性疾病开发新的治疗和预防疗法。

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