Hepatitis C virus (HCV) infection is a major cause of chronic liver diseases such as steatosis, cirrhosis, and hepatocellular carcinoma. HCV particles have been found to associate with apolipoproteins, and apolipoproteins not only participate in the HCV life cycle, but also help HCV escape recognition by the host immune system, which pose challenges for the development of both HCV treatments and vaccines. However, no study has reported on the comprehensive identification of apolipoprotein associations with HCV particles. In the present study, we performed proteome analysis by affinity purification coupled with mass spectrometry (AP-MS) to comprehensively identify the apolipoprotein associations with HCV particles, and ApoM was first identified by AP-MS besides the previously reported ApoE, ApoB, ApoA-I and ApoC-I. Additionally, three assays further confirmed that ApoM was a novel virus particle associated protein. We also showed that ApoM was required for HCV production, especially for the assembly/release step of HCV life cycle. Furthermore, ApoM interacted with the HCV E2 protein. Finally, HCV infection reduced ApoM expression both in vitro and in vivo. Collectively, our study demonstrates that ApoM, identified as a novel HCV particle associated protein, contributes to HCV assembly/release and interacts with HCV E2 protein. It provides new insights on how HCV and the host apolipoproteins are reciprocally influenced and lays a basis for research in developing innovative antiviral strategies.

中文翻译：

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载脂蛋白M被鉴定为新型丙型肝炎病毒（HCV）颗粒相关蛋白，可促进HCV装配并与E2蛋白相互作用。

丙型肝炎病毒（HCV）感染是慢性肝脏疾病（例如脂肪变性，肝硬化和肝细胞癌）的主要原因。已经发现HCV颗粒与载脂蛋白相关，并且载脂蛋白不仅参与HCV的生命周期，而且帮助HCV逃脱宿主免疫系统的识别，这对HCV治疗和疫苗的开发提出了挑战。但是，尚无关于将载脂蛋白与HCV颗粒结合的综合鉴定的研究报告。在本研究中，我们通过亲和纯化与质谱（AP-MS）结合进行蛋白质组分析，以全面鉴定与HCV颗粒的载脂蛋白缔合，除先前报道的ApoE，ApoB，ApoA-我和ApoC-I。另外，三种测定进一步证实ApoM是一种新型的病毒颗粒相关蛋白。我们还表明，HCV生产需要ApoM，尤其是HCV生命周期的组装/发布步骤。此外，ApoM与HCV E2蛋白相互作用。最后，HCV感染在体外和体内都降低了ApoM的表达。总体而言，我们的研究表明，被鉴定为新型HCV颗粒相关蛋白的ApoM有助于HCV组装/释放并与HCV E2蛋白相互作用。它提供了关于HCV和宿主载脂蛋白如何相互影响的新见解，并为开发创新抗病毒策略的研究奠定了基础。特别是在HCV生命周期的组装/发布步骤中。此外，ApoM与HCV E2蛋白相互作用。最后，HCV感染在体外和体内都降低了ApoM的表达。总体而言，我们的研究表明，被鉴定为新型HCV颗粒相关蛋白的ApoM有助于HCV组装/释放并与HCV E2蛋白相互作用。它提供了关于如何相互影响HCV和宿主载脂蛋白的新见解，并为开发创新抗病毒策略的研究奠定了基础。特别是在HCV生命周期的组装/发布步骤中。此外，ApoM与HCV E2蛋白相互作用。最后，HCV感染在体外和体内都降低了ApoM的表达。总体而言，我们的研究表明，被鉴定为新型HCV颗粒相关蛋白的ApoM有助于HCV组装/释放并与HCV E2蛋白相互作用。它提供了关于如何相互影响HCV和宿主载脂蛋白的新见解，并为开发创新抗病毒策略的研究奠定了基础。