新城疫病毒M蛋白与宿主蛋白相互作用的研究进展

doi:10.11843/j.issn.0366-6964.2022.01.004

摘要/Abstract

摘要： 新城疫病毒（Newcastle disease virus，NDV）是单股负链不分节段的RNA病毒，其基因组大小约为15.2 kb，编码6种结构蛋白和2种非结构蛋白。由于NDV基因组较小，不能编码病毒复制需要的所有蛋白，因此必须借助宿主蛋白来完成NDV的生活周期。M蛋白是一种非糖基化膜相关蛋白，在抑制宿主细胞基因转录、调节病毒基因组复制和转录、促进子代病毒粒子组装和出芽等方面具有重要作用。目前，国内外在M蛋白与NDV毒力和复制的关系，以及以M蛋白为核心的病毒样颗粒形成和利用方面取得了较大的研究进展，但是对M蛋白与宿主蛋白相互作用以及M蛋白如何调控NDV的复制研究进展相对缓慢。鉴于M蛋白在NDV复制中的重要作用，本文主要从M蛋白的结构特征和细胞内定位特征，以及M蛋白与宿主蛋白相互作用的功能研究方面进行综述，以期为更好地认识和研究M蛋白在NDV复制和致病性中的作用提供参考。

关键词: 新城疫病毒, M蛋白, 宿主蛋白, 蛋白相互作用, 病毒复制

Abstract: Newcastle disease virus (NDV) is a kind of single-stranded negative-sense non-segmented RNA virus, which contains the genome size of about 15.2 kb in length that encodes six structural proteins and two non-structural proteins. Since the NDV genome is smaller, it cannot encode all the proteins needed for viral replication, thus host proteins must be employed to complete the life cycle of NDV. The NDV M protein is a non-glycosylated membrane-associated protein, which plays essential roles in inhibiting host cell gene transcription, regulating the replication and transcription of the NDV genome, and promoting the assembly and budding of progeny virions. At present, great research progresses have been made in the relationship between M protein and NDV virulence and replication, and the formation and utilization of M protein-based virus-like particles. However, there has little progress about the roles of NDV M protein interaction with host proteins in regulating NDV replication. Due to the crucial roles of M protein in NDV replication, this summary mainly reviews the structural characteristics and intracellular localization characteristics of M protein, and also the functional study on the interactions between M protein and host proteins, which will provide theoretical references for better understanding and studying the role of M protein in the replication and pathogenicity of NDV.

Key words: Newcastle disease virus, M protein, host protein, protein-protein interaction, virus replication

中图分类号:

段志强, 谢玲玲, 陈佳琪, 唐宏, 王燕碧, 赵采芹, 赵佳福. 新城疫病毒M蛋白与宿主蛋白相互作用的研究进展[J]. 畜牧兽医学报, 2022, 53(1): 32-42.

DUAN Zhiqiang, XIE Lingling, CHEN Jiaqi, TANG Hong, WANG Yanbi, ZHAO Caiqin, ZHAO Jiafu. Research Progress on the Interactions of Newcastle Disease Virus M Protein with Host Proteins[J]. Acta Veterinaria et Zootechnica Sinica, 2022, 53(1): 32-42.

参考文献 80

[1]	AMARASINGHE G K, AYLLÓN M A, BÀO Y, et al. Taxonomy of the order Mononegavirales:update 2019[J]. Arch Virol, 2019, 164(7):1967-1980.
[2]	BATTISTI A J, MENG G, WINKLER D C, et al. Structure and assembly of a paramyxovirus matrix protein[J]. Proc Natl Acad Sci U S A, 2012, 109(35):13996-14000.
[3]	COLEMAN N A, PEEPLES M E. The matrix protein of Newcastle disease virus localizes to the nucleus via a bipartite nuclear localization signal[J]. Virology, 1993, 195(2):596-607.
[4]	DUAN Z Q, DENG S S, JI X Q, et al. Nuclear localization of Newcastle disease virus matrix protein promotes virus replication by affecting viral RNA synthesis and transcription and inhibiting host cell transcription[J]. Vet Res, 2019, 50(1):22.
[5]	DUAN Z Q, SONG Q Q, WANG Y Y, et al. Characterization of signal sequences determining the nuclear export of Newcastle disease virus matrix protein[J]. Arch Virol, 2013, 158(12):2589-2595.
[6]	PANTUA H D, MCGINNES L W, PEEPLES M E, et al. Requirements for the assembly and release of Newcastle disease virus-like particles[J]. J Virol, 2006, 80(22):11062-11073.
[7]	DUAN Z Q, LI J, ZHU J, et al. A single amino acid mutation, R42A, in the Newcastle disease virus matrix protein abrogates its nuclear localization and attenuates viral replication and pathogenicity[J]. J Gen Virol, 2014, 95(5):1067-1073.
[8]	XU H X, SONG Q Q, ZHU J, et al. A single R36Q mutation in the matrix protein of pigeon paramyxovirus type 1 reduces virus replication and shedding in pigeons[J]. Arch Virol, 2016, 161(7):1949-1955.
[9]	XU H X, DUAN Z Q, CHEN Y, et al. Simultaneous mutation of G275A and P276A in the matrix protein of Newcastle disease virus decreases virus replication and budding[J]. Arch Virol, 2016, 161(12):3527-3533.
[10]	段志强, 嵇辛勤, 邓珊珊, 等. 鸭源新城疫病毒M蛋白核定位信号突变影响病毒的毒力和复制能力[J]. 微生物学报, 2018, 58(10):1786-1797.DUAN Z Q, JI X Q, DENG S S, et al. Nuclear localization signal mutation in the M protein attenuates the virulence and replication of duck-origin Newcastle disease virus[J]. Acta Microbiologica Sinica, 2018, 58(10):1786-1797. (in Chinese)
[11]	XU X H, DING Z, LI J D, et al. Newcastle disease virus-like particles containing the Brucella BCSP31 protein induce dendritic cell activation and protect mice against virulent Brucella challenge[J]. Vet Microbiol, 2019, 229:39-47.
[12]	XU X H, QIAN J, QIN L S, et al. Chimeric Newcastle disease virus-like particles containing DC-binding peptide-fused haemagglutinin protect chickens from virulent Newcastle disease virus and H9 N2 avian influenza virus challenge[J]. Virol Sin, 2020, 35(4):455-467.
[13]	YANG Y P, SHI W, ABIONA O M, et al. Newcastle disease virus-like particles displaying prefusion-stabilized SARS-CoV-2 spikes elicit potent neutralizing responses[J]. Vaccines (Basel), 2021, 9(2):73.
[14]	CHAMBERS P, MILLAR N S, PLATT S G, et al. Nucleotide sequence of the gene encoding the matrix protein of Newcastle disease virus[J]. Nucl Acids Res, 1986, 14(22):9051-9061.
[15]	姜维雨. 新城疫病毒M蛋白K119和K260泛素化修饰有助于病毒样颗粒的形成[D]. 上海: 中国农业科学院, 2019.JIANG W Y. K119 and K260 ubiquitination of Newcastle disease virus M protein is essential for efficient virus-like particle formation[D]. Shanghai: Chinese Academy of Agricultural Sciences, 2019. (in Chinese)
[16]	彭听雨, 杨冰欢, 谭磊, 等. 新城疫病毒M蛋白247位赖氨酸对其功能的影响[J/OL]. 中国动物传染病学报, 2021:1-10. (2021-04-27). http://kns. cnki. net/kcms/detail/31. 2031.S. 20210427. 1012. 010.html. PENG T Y, YANG B H, TAN L, et al. Effect of 247 lysine in Newcastle disease virus matrix protein on its functions[J/OL]. Chinese Journal of Animal Infectious Diseases, 2021:1-10. (2021-04-27). http://kns. cnki. net/kcms/detail/31. 2031.S. 20210427. 1012. 010.html.(in Chinese)
[17]	董靖. 新城疫病毒M蛋白单克隆抗体制备及核定位研究[D]. 合肥: 安徽农业大学, 2020.DONG J. Establishment of monoclonal antibodies against Newcastle disease virus matrix protein and its nuclear localization[D]. Hefei: Anhui Agricultural University. (in Chinese)
[18]	BI Y K, JIN Z Y, WANG Y H, et al. Identification of two distinct linear B cell epitopes of the matrix protein of the Newcastle disease virus vaccine strain LaSota[J]. Viral Immunol, 2019, 32(5):221-229.
[19]	EL NAJJAR F, SCHMITT A P, DUTCH R E. Paramyxovirus glycoprotein incorporation, assembly and budding:a three way dance for infectious particle production[J]. Viruses, 2014, 6(8):3019-3054.
[20]	SHTYKOVA E V, PETOUKHOV M V, DADINOVA L A, et al. Solution structure, self-assembly, and membrane interactions of the matrix protein from Newcastle disease virus at neutral and acidic pH[J]. J Virol, 2019, 93(6):e01450-18.
[21]	SÁNCHEZ-FELIPE L, VILLAR E, MUOZ-BARROSO I. Entry of Newcastle disease virus into the host cell:role of acidic pH and endocytosis[J]. Biochim Biophys Acta, 2014, 1838(1):300-309.
[22]	ZHAO R, SHI Q K, HAN Z X, et al. Newcastle disease virus entry into chicken macrophages via a pH-dependent, dynamin and caveola-mediated endocytic pathway that requires Rab5[J]. J Virol, 2021, 95(13):e0228820.
[23]	FAABERG K S, PEEPLES M E. Strain variation and nuclear association of Newcastle disease virus matrix protein[J]. J Virol, 1988, 62(2):586-593.
[24]	PEEPLES M E, WANG C, GUPTA K C, et al. Nuclear entry and nucleolar localization of the Newcastle disease virus (NDV) matrix protein occur early in infection and do not require other NDV proteins[J]. J Virol, 1992, 66(5):3263-3269.
[25]	DUAN Z Q, LI Q H, HE L, et al. Application of green fluorescent protein-labeled assay for the study of subcellular localization of Newcastle disease virus matrix protein[J]. J Virol Methods, 2013, 194(1-2):118-122.
[26]	WOLFF B, PARK M K, KLIMA E, et al. Antibodies against the SV40 large T antigen nuclear localization sequence[J]. Arch Biochem Biophys, 1991, 288(1):131-140.
[27]	PAINE P L, YASSIN R, PAINE T M, et al. Intranuclear binding on nucleoplasmin[J]. J Cell Biochem, 1995, 58(1):105-114.
[28]	FUNG H Y J, NIESMAN A, CHOOK Y M. An update to the CRM1 cargo/NES database NESdb[J]. Mol Biol Cell, 2021, 32(6):467-469.
[29]	DUAN Z Q, CHEN J, XU H X, et al. The nucleolar phosphoprotein B23 targets Newcastle disease virus matrix protein to the nucleoli and facilitates viral replication[J]. Virology, 2014, 452-453:212-222.
[30]	BURMAN B, PESCI G, ZAMARIN D. Newcastle disease virus at the forefront of cancer immunotherapy[J]. Cancers (Basel), 2020, 12(12):3552.
[31]	REN S H, REHMAN Z U, SHI M Y, et al. Hemagglutinin-neuraminidase and fusion proteins of virulent Newcastle disease virus cooperatively disturb fusion-fission homeostasis to enhance mitochondrial function by activating the unfolded protein response of endoplasmic reticulum and mitochondrial stress[J]. Vet Res, 2019, 50(1):37.
[32]	REN S H, UR REHMAN Z, GAO B, et al. ATM-mediated DNA double-strand break response facilitated oncolytic Newcastle disease virus replication and promoted syncytium formation in tumor cells[J]. PLoS Pathog, 2020, 16(6):e1008514.
[33]	CHENG J H, SUN Y J, ZHANG F Q, et al. Newcastle disease virus NP and P proteins induce autophagy via the endoplasmic reticulum stress-related unfolded protein response[J]. Sci Rep, 2016, 6:24721.
[34]	GRAY Z, TABARRAEI A, MORADI A, et al. M51R and Delta-M51 matrix protein of the vesicular stomatitis virus induce apoptosis in colorectal cancer cells[J]. Mol Biol Rep, 2019, 46(3):3371-3379.
[35]	KOJIMA I, IZUMI F, OZAWA M, et al. Analyses of cell death mechanisms related to amino acid substitution at position 95 in the rabies virus matrix protein[J]. J Gen Virol, 2021, 102(4):001594, doi:10. 1099/jgv. 0. 001594.
[36]	MOLOUKI A, HSU Y T, JAHANSHIRI F, et al. The matrix (M) protein of Newcastle disease virus binds to human bax through its BH3 domain[J]. Virol J, 2011, 8:385.
[37]	GHILDYAL R, HO A, JANS D A. Central role of the respiratory syncytial virus matrix protein in infection[J]. FEMS Microbiol Rev, 2006, 30(5):692-705.
[38]	HARRISON M S, SAKAGUCHI T, SCHMITT A P. Paramyxovirus assembly and budding:building particles that transmit infections[J]. Int J Biochem Cell Biol, 2010, 42(9):1416-1429.
[39]	PENTECOST M, VASHISHT A A, LESTER T, et al. Evidence for ubiquitin-regulated nuclear and subnuclear trafficking among Paramyxovirinae matrix proteins[J]. PLoS Pathog, 2015, 11(3):e1004739.
[40]	YU X L, SHAHRIARI S, LI H M, et al. Measles virus matrix protein inhibits host cell transcription[J]. PLoS One, 2016, 11(8):e0161360.
[41]	DONNELLY C M, ROBY J A, SCOTT C J, et al. The structural features of Henipavirus matrix protein driving intracellular trafficking[J]. Viral Immunol, 2021, 34(1):27-40.
[42]	DENIS G V, MCCOMB M E, FALLER D V, et al. Identification of transcription complexes that contain the double bromodomain protein Brd2 and chromatin remodeling machines[J]. J Proteome Res, 2006, 5(3):502-511.
[43]	ZHOU L, HAN Y F, YUAN C, et al. Screening and bioinformatics analysis of cellular proteins interacting with chicken bromodomain-containing protein 2 in DF-1 cells[J]. Br Poult Sci, 2021:1-10.doi:10. 1080/00071668. 2021. 1943311.
[44]	周磊, 韩一帆, 段志强. 含溴结构域蛋白2结构与功能的研究进展[J]. 中国细胞生物学学报, 2021, 43(4):856-865.ZHOU L, HAN Y F, DUAN Z Q. Advances in the structure and function of bromodomain-containing protein 2[J]. Chinese Journal of Cell Biology, 2021, 43(4):856-865. (in Chinese)
[45]	DUAN Z Q, HAN Y F, ZHOU L, et al. Chicken bromodomain-containing protein 2 interacts with the Newcastle disease virus matrix protein and promotes viral replication[J]. Vet Res, 2020, 51(1):120.
[46]	FU X K, LIANG C, LI F F, et al. The rules and functions of nucleocytoplasmic shuttling proteins[J]. Int J Mol Sci, 2018, 19(5):1445.
[47]	PACI G, ZHENG T T, CARIA J, et al. Molecular determinants of large cargo transport into the nucleus[J]. Elife, 2020, 9:e55963.
[48]	DUAN Z Q, XU H X, JI X Q, et al. Importin α5 negatively regulates importin β1-mediated nuclear import of Newcastle disease virus matrix protein and viral replication and pathogenicity in chicken fibroblasts[J]. Virulence, 2018, 9(1):783-803.
[49]	WANG A Y, LIU H T. The past, present, and future of CRM1/XPO1 inhibitors[J]. Stem Cell Investig, 2019, 6:6.
[50]	SALVETTI A, GRECO A. Viruses and the nucleolus:the fatal attraction[J]. Biochim Biophys Acta Mol Basis Dis, 2014, 1842(6):840-847.
[51]	RAWLINSON S M, MOSELEY G W. The nucleolar interface of RNA viruses[J]. Cell Microbiol, 2015, 17(8):1108-1120.
[52]	ZHOU J W, DAI Y D, LIN C, et al. Nucleolar protein NPM1 is essential for circovirus replication by binding to viral capsid[J]. Virulence, 2020, 11(1):1379-1393.
[53]	DONG D D, ZHU S Q, MIAO Q H, et al. Nucleolin (NCL) inhibits the growth of peste des petits ruminants virus[J]. J Gen Virol, 2020, 101(1):33-43.
[54]	CHEN G Q, YAN Q, WANG H R, et al. Identification and characterization of the nucleolar localization signal of Autographa Californica multiple nucleopolyhedrovirus LEF5[J]. J Virol, 2020, 94(4):e01891-19.
[55]	段志强, 谢玲玲, 周迪, 等. 新城疫病毒M蛋白细胞核定位的机制与功能研究进展[J]. 畜牧兽医学报, 2021, 52(4):891-898.DUAN Z Q, XIE L L, ZHOU D, et al. Research progress on the mechanism and function of nuclear localization of Newcastle disease virus M protein[J]. Acta Veterinaria et Zootechnica Sinica, 2021, 52(4):891-898. (in Chinese)
[56]	GIUFFRE R M, TOVELL D R, KAY C M, et al. Evidence for an interaction between the membrane protein of a paramyxovirus and actin[J]. J Virol, 1982, 42(3):963-968.
[57]	REN X P, XUE C Y, KONG Q M, et al. Proteomic analysis of purified Newcastle disease virus particles[J]. Proteome Sci, 2012, 10(1):32.
[58]	KOGA R, KUBOTA M, HASHIGUCHI T, et al. Annexin A2 mediates the localization of measles virus matrix protein at the plasma membrane[J]. J Virol, 2018, 92(10):e00181-18.
[59]	VIETRI M, RADULOVIC M, STENMARK H. The many functions of ESCRTs[J]. Nat Rev Mol Cell Biol, 2020, 21(1):25-42.
[60]	MENG B, LEVER A M L. The interplay between ESCRT and viral factors in the enveloped virus life cycle[J]. Viruses, 2021, 13(2):324.
[61]	DUAN Z Q, HU Z L, ZHU J, et al. Mutations in the FPIV motif of Newcastle disease virus matrix protein attenuate virus replication and reduce virus budding[J]. Arch Virol, 2014, 159(7):1813-1819.
[62]	LATA S, SCHOEHN G, SOLOMONS J, et al. Structure and function of ESCRT-III[J]. Biochem Soc Trans, 2009, 37(1):156-160.
[63]	LI X, LI X Q, CAO H, et al. Engagement of new castle disease virus (NDV) matrix (M) protein with charged multivesicular body protein (CHMP) 4 facilitates viral replication[J]. Virus Res, 2013, 171(1):80-88.
[64]	BEN KHALIFA Y, LUCO S, BESSON B, et al. The matrix protein of rabies virus binds to RelAp43 to modulate NF-κB-dependent gene expression related to innate immunity[J]. Sci Rep, 2016, 6:39420.
[65]	MARQUIS K A, BECKER R L, WEISS A N, et al. The VSV matrix protein inhibits NF-κB and the interferon response independently in mouse L929 cells[J]. Virology, 2020, 548:117-123.
[66]	HUI X F, ZHANG L L, CAO L, et al. SARS-CoV-2 promote autophagy to suppress type I interferon response[J]. Sig Transduct Target Ther, 2021, 6(1):180.
[67]	王蕾, 陈福勇, 郑世军, 等. 新城疫病毒(NDV)基质(M)蛋白在体外对炎症因子诱导的作用[J]. 中国兽医杂志, 2008, 44(4):14-15.WANG L, CHEN F Y, ZHENG S J, et al. Induction effect of Newcastle disease virus (NDV) matrix (M) protein on the production of inflammatory factors in vitro[J]. Chinese Journal of Veterinary Medicine, 2008, 44(4):14-15. (in Chinese).
[68]	DUAN Z Q, YUAN C, HAN Y F, et al. TMT-based quantitative proteomics analysis reveals the attenuated replication mechanism of Newcastle disease virus caused by nuclear localization signal mutation in viral matrix protein[J]. Virulence, 2020, 11(1):607-635.
[69]	NG L F P, HISCOX J A. Viperin poisons viral replication[J]. Cell Host & Microbe, 2018, 24(2):181-183.
[70]	YUAN Y K, MIAO Y, QIAN L P, et al. Targeting UBE4A revives viperin protein in epithelium to enhance host antiviral defense[J]. Mol Cell, 2020, 77(4):734-747.
[71]	SHAH M, BHARADWAJ M S K, GUPTA A, et al. Chicken viperin inhibits Newcastle disease virus infection in vitro:A possible interaction with the viral matrix protein[J]. Cytokine, 2019, 120:28-40.
[72]	BECK S, ZICKLER M, PINHO DOS REIS V, et al. ANP32B deficiency protects mice from lethal influenza A virus challenge by dampening the host immune response[J]. Front Immunol, 2020, 11:450.
[73]	GÜNTHER M, BAUER A, MVLLER M, et al. Interaction of host cellular factor ANP32B with matrix proteins of different paramyxoviruses[J]. J Gen Virol, 2020, 101(1):44-58.
[74]	RAJANI K R, KNELLER E L P, MCKENZIE M O, et al. Complexes of vesicular stomatitis virus matrix protein with host Rae1 and Nup98 involved in inhibition of host transcription[J]. PLoS Pathog, 2012, 8(9):e1002929.
[75]	QUAN B L, SEO H S, BLOBEL G, et al. Vesiculoviral matrix (M) protein occupies nucleic acid binding site at nucleoporin pair (Rae1·Nup98)[J]. Proc Natl Acad Sci U S A, 2014, 111(25):9127-9132.
[76]	BEILSTEIN F, OBIANG L, RAUX H, et al. Characterization of the interaction between the matrix protein of vesicular stomatitis virus and the immunoproteasome subunit LMP2[J]. J Virol, 2015, 89(21):11019-11029.
[77]	PAN W, SONG D G, HE W Q, et al. EIF3i affects vesicular stomatitis virus growth by interacting with matrix protein[J]. Vet Microbiol, 2017, 212:59-66.
[78]	PEI Z F, BAI Y T, SCHMITT A P. PIV5 M protein interaction with host protein angiomotin-like 1[J]. Virology, 2010, 397(1):155-166.
[79]	RAY G, SCHMITT P T, SCHMITT A P. Angiomotin-like 1 links paramyxovirus M proteins to NEDD4 family ubiquitin ligases[J]. Viruses, 2019, 11(2):128.
[80]	段云兵. 新城疫病毒基质(M)蛋白生物学功能的初步研究[D]. 南京: 南京农业大学, 2014.DUAN Y B. Preliminary study on biological functions of Newcastle disease virus matrix protein[D]. Nanjing: Nanjing Agricultural University, 2014.