Host Cell Protein MCM7 Interacts with NP1 of Minute Virus of Canines and Facilitates Viral DNA Replication.

IF 4.2 2区 生物学 Q2 MICROBIOLOGY
Zhiping Hei, Xiang Ren, Kai Ji, Zhijie Zhang, Binghan Chen, Yuning Sun
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引用次数: 0

Abstract

Minute virus of canines (MVC), which is a member of the Bocaparvovirus genus, is a non-enveloped, single-stranded DNA virus that causes respiratory and gastrointestinal disease in canines, as well as causing infertility and fetal death in pregnant dogs. The non-structural small protein NP1 of bocaparvoviruses is a unique feature that distinguishes the bocaparvovirus subfamily from other parvovirus subfamilies. In the life cycle of the MVC, NP1 plays an indispensable role in viral DNA replication and pre-mRNA processing. Currently, there is a paucity of studies reporting the characterization of host cell proteins interacting with NP1 during MVC replication. In this study, we screened and identified host cell proteins interacting with MVC-NP1 through immunoprecipitation (IP) combined with liquid chromatography and tandem mass spectrometry (LC-MS/MS) analysis; MCM7 (Mini-chromosome Maintenance Protein 7) has been identified and confirmed to interact directly with NP1 through its N-terminal domain. Furthermore, functional studies reveal that MCM7 is essential in MVC replication. The knockdown of MCM7 decreased the expression of this MVC protein significantly, as well as suppressing MVC replication by arresting the cell cycle in the G0/G1 phase during infection. Conversely, up-regulating MCM7 can rehabilitate the expression of MVC proteins, as well as supporting MVC replication. In conclusion, this study elucidates the interaction between the NP1 protein of MVC and the host factor MCM7, demonstrating that MCM7 is a key factor in the replication process of MVC. These findings provide a potential target for future antiviral therapy.

宿主细胞蛋白MCM7与犬细小病毒NP1相互作用并促进病毒DNA复制
犬细小病毒(MVC)是Bocaparvovirus属的一种成员,是一种无包膜单链DNA病毒,可引起犬类呼吸道和胃肠道疾病,并可导致怀孕犬的不育和胎儿死亡。bocaparvovirus的非结构小蛋白NP1是bocaparvovirus亚家族区别于其他细小病毒亚家族的一个独特特征。在MVC的生命周期中,NP1在病毒DNA复制和pre-mRNA加工中起着不可或缺的作用。目前,关于在MVC复制过程中与NP1相互作用的宿主细胞蛋白特征的研究还很缺乏。在本研究中,我们通过免疫沉淀(IP)结合液相色谱和串联质谱(LC-MS/MS)分析,筛选和鉴定了与MVC-NP1相互作用的宿主细胞蛋白;MCM7 (mini -染色体维持蛋白7)已被鉴定并证实通过其n端结构域直接与NP1相互作用。此外,功能研究表明MCM7在MVC复制中是必不可少的。MCM7的敲除显著降低了该MVC蛋白的表达,并通过在感染期间阻断G0/G1期的细胞周期来抑制MVC复制。相反,上调MCM7可以恢复MVC蛋白的表达,并支持MVC复制。综上所述,本研究阐明了MVC的NP1蛋白与宿主因子MCM7之间的相互作用,表明MCM7是MVC复制过程中的关键因子。这些发现为未来抗病毒治疗提供了一个潜在的靶点。
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来源期刊
Microorganisms
Microorganisms Medicine-Microbiology (medical)
CiteScore
7.40
自引率
6.70%
发文量
2168
审稿时长
20.03 days
期刊介绍: Microorganisms (ISSN 2076-2607) is an international, peer-reviewed open access journal which provides an advanced forum for studies related to prokaryotic and eukaryotic microorganisms, viruses and prions. It publishes reviews, research papers and communications. Our aim is to encourage scientists to publish their experimental and theoretical results in as much detail as possible. There is no restriction on the length of the papers. The full experimental details must be provided so that the results can be reproduced. Electronic files and software regarding the full details of the calculation or experimental procedure, if unable to be published in a normal way, can be deposited as supplementary electronic material.
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