猴痘病毒B.1谱系遗传分支、毒力基因及蛋白功能

doi:10.3969/j.issn.1672-2302.2024.01.001

摘要/Abstract

摘要：

2022年以来，猴痘疫情在全球暴发和流行。相较以往的猴痘病毒，2022年流行的猴痘毒株传播能力和宿主适应性等明显增强，猴痘B.1谱系毒株已成为全球猴痘疫情流行的主要毒株。为此，本文对猴痘病毒B.1谱系遗传分支、毒力基因及蛋白功能进行综述，并就部分基因产物的蛋白功能进行了注释，以期为猴痘疫情的科学防控提供参考。

关键词: 猴痘病毒, B.1谱系毒株, 遗传分支, 毒力基因, 蛋白功能

Abstract:

Mpox virus has been outbreak and prevalent in many countries worldwide since 2022. Compared with the previous mpox virus strains, the 2022 epidemic mpox strains had gained significantly enhanced transmission ability and host adaptability, and the mpox lineage B.1 strains had become the dominant strains in the global epidemic of mpox. In this paper, we reviewed the genetic branches, virulence genes and protein functions of the mpox B.1 strains, and annotated the protein functions of some of the gene products, with an attempt to provide reference for the scientific prevention and control of mpox epidemics.

Key words: Mpox virus, Lineage B.1 strain, Genetic branches, Virulence gene, Protein function

中图分类号:

R511

林思宇, 陈芳, 罗语思, 张科. 猴痘病毒B.1谱系遗传分支、毒力基因及蛋白功能[J]. 热带病与寄生虫学, 2024, 22(1): 1-6.

LIN Siyu, CHEN Fang, LUO Yusi, ZHANG Ke. Genetic branches, virulence genes, and protein functions of the mpox virus lineage B.1[J]. Journal of Tropical Diseases and Parasitology, 2024, 22(1): 1-6.

图/表 4

表1

猴痘病毒毒力基因和基因编码蛋白及其功能

基因 / 编码蛋白	碱基数 / 氨基酸数	编码蛋白功能
A33R / 细胞外包膜特异性蛋白	429 / 142	促进病毒结合、融合和进入靶细胞^[21]
A32L / OPG157蛋白	234 / 77	编码OPG157蛋白，与牛痘病毒A30L蛋白同源，是致密病毒质与病毒包膜结合，形成成熟病毒颗粒必需的蛋白^[22]
A37R / A37R蛋白	531 / 176	编码A37R蛋白，与牛痘病毒A35R蛋白同源，A35R蛋白影响宿主抗原递呈细胞表面MHC Ⅱ类分子的表达^[23]，但目前A37R蛋白功能未知
A43R / 膜糖蛋白	594 / 197	识别抗原和免疫作用^[24]
A44R / A44R蛋白	225 / 74	蛋白功能尚不清楚，但A44R含有赖氨酸和天冬氨酸残基，是由盐键形成的稳定发夹折叠结构^[25]
A45L / 3-β-羟基-δ5-类固醇脱氢酶	1 041 / 346	调节激素合成和代谢^[6]
A47R / IL-1信号抑制器	723 / 240	抑制IL-1的作用^[6]
A51R/ OPG181蛋白	1 005 / 3 341	编码OPG181蛋白，与牛痘病毒A51同源，OPG181蛋白能与泛素结合，参与维持病毒蛋白稳定性和病毒复制^[26]
B4R / Schlafen样蛋白	1 512 / 503	抑制宿主细胞增殖，调控造血细胞，调节免疫应答等^[24]
B5R / 锚蛋白	1 686 / 561	参与宿主细胞黏附、信号传导以及mRNA转录等^[24]
B7R / 膜蛋白	531 / 176	识别抗原和免疫作用^[6]
B8R / 毒力因子，内质网驻留蛋白	549 / 182	参与蛋白质的折叠和组装等^[6]
B10R / 纤维瘤T4样蛋白	666 / 221	抑制淋巴细胞凋亡^[6]
B11R / 蛋白激酶样蛋白	849 / 282	参与细胞内信号传导^[6]
B12R / 丝氨酸蛋白酶抑制剂	1 035 / 344	抑制丝氨酸蛋白酶活性和IL-1β转化酶^[6]
B13R / IL-1结合蛋白抑制剂	450 / 149	抑制IL-1结合蛋白^[6]
B14R / IL-1β结合蛋白	981 / 326	阻止IL-1β与IL-1受体结合并激活与细胞凋亡相关信号^[6]
B16R / 干扰素-a/β（IFN-a/β）结合蛋白	1 059 / 352	调节细胞分化，参与宿主细胞增殖、先天性和适应性免疫^[6]
B17R / 锚蛋白	2 382 / 793	参与宿主细胞黏附、信号传导以及mRNA转录等^[6]
B19R / 丝氨酸蛋白酶抑制剂	1 074 / 357	拮抗丝氨酸蛋白酶活性，参与凝血、纤溶和程序性细胞死亡等生物过程^[6]
B20R / 膜蛋白	573 / 190	识别抗原和免疫作用^[6]
B21R / 膜糖蛋白	5 640 / 1 879	识别抗原和免疫作用^[6]
C1L / 宿主范围因子，锚蛋白	855 / 284	调节靶细胞酶活性，抑制宿主细胞凋亡；参与宿主细胞黏附、信号传导以及mRNA转录等^[6]
C2L / 丝氨酸蛋白酶抑制剂	1 128 / 375	拮抗丝氨酸蛋白酶活性，抑制宿主细胞融合^[6]
C4L / 磷脂酶D类蛋白	1 275 / 424	参与调控宿主细胞脂质代谢、信号传导、生物膜形成等生理生化过程^[6]
C5L / 磷脂酶B类蛋白	831 / 276	参与多种宿主细胞信号传导，调节细胞增殖分化^[6]
C6R / IL-1结合蛋白抑制剂	450 / 149	抑制IL-1结合蛋白功能^[6]
C7L / 细胞凋亡抑制剂	660 / 219	抑制宿主细胞凋亡^[6]
C9L / Kelch样蛋白	1 464 / 487	参与蛋白质泛素化修饰^[24]
C11L / 膜蛋白	1 032 / 343	识别抗原和免疫作用^[6]
D1L / 锚蛋白	1 314 / 437	参与宿主细胞黏附、信号传导以及mRNA转录等^[6]
D3R / EGF样生长因子	429 / 142	调节细胞增殖和分化^[6]
D5R / 锌指蛋白，毒力因子	729 / 242	抑制紫外线诱导的细胞凋亡^[6]
D7L / 宿主范围因子，锚蛋白	1 983 / 660	调节靶细胞酶活性，抑制细胞凋亡；参与宿主细胞黏附、信号传导以及mRNA转录等^[6]
D9L / 锚蛋白	1 893 / 630	参与宿主细胞黏附、信号传导以及mRNA转录等^[6]
D10L / 宿主范围因子	453 / 150	调节靶细胞酶活性，抑制宿主细胞凋亡等^[6]
D11L / 核苷三磷酸水解酶	462 / 153	水解核苷三磷酸^[27]
D12L / Kelch样蛋白	621 / 206	参与蛋白质泛素化修饰^[24]
D13L / IL-1β拮抗剂	948 / 315	抑制IL-1作用，阻止IL-1与受体结合^[6]
D14L / 补体结合蛋白	651 / 216	猴痘补体酶抑制剂^[6]
H3L / IMV肝素结合表面膜蛋白	975 / 324	调节单核巨噬细胞功能，通过线粒体途径调节宿主细胞凋亡^[24]
J1L / CC趋化因子结合蛋白	741 / 246	启动CC趋化因子结合活性和CC趋化因子受体活性^[6]
J2L / TNF结合蛋白	1 047 / 348	抑制TNF活性，抑制其细胞毒活性和诱导IL-1产生^[6]
J3L / 锚蛋白	1 764 / 587	参与宿主细胞黏附、信号传导以及mRNA转录等^[6]
N1R / IL-1结合蛋白抑制剂	462 / 153	抑制IL-1结合蛋白^[28]
O1L / 锚蛋白	1 329 / 442	参与宿主细胞黏附、信号传导以及mRNA转录等^[16]
P2L / a-鹅膏菌素敏感性蛋白	534 / 177	RNA聚合酶Ⅱ特异性抑制剂^[5]

表1

图1

图2

图3

参考文献 34

[1]	蔡鹏, 殷建华, 张宏伟. 猴痘病原学、流行病学特征及其防控策略[J]. 上海预防医学, 2022, 34(10):1044-1052.
[2]	段曰黎, 王新宇. 猴痘的流行病学及防治进展[J]. 复旦学报(医学版), 2023, 50(6):906-910,927.
[3]	姚开虎. 知往鉴今:人感染猴痘史及其非同寻常的2022年多国暴发疫情[J]. 中国当代儿科杂志, 2022, 24(7):717-727.
[4]	Alakunle E, Moens U, Nchinda G, et al. Monkeypox virus in Nigeria: infection biology, epidemiology, and evolution[J]. Viruses, 2020, 12(11):1257. doi: 10.3390/v12111257 URL
[5]	Di Giulio DB, Eckburg PB. Human monkeypox: an emerging zoonosis[J]. Lancet Infect Dis, 2004, 4(1):15-25. doi: 10.1016/s1473-3099(03)00856-9 pmid: 14720564
[6]	Chen NH, Li GY, Liszewski MK, et al. Virulence differences between monkeypox virus isolates from West Africa and the Congo Basin[J]. Virology, 2005, 340(1):46-63. doi: 10.1016/j.virol.2005.05.030 pmid: 16023693
[7]	韩辉, 伍波, 刘莉, 等. 2022年全球多国猴痘暴发疫情风险评估[J]. 口岸卫生控制, 2022, 27(3):1-5,17.
[8]	汪慧, 钟贤武, 李意兰, 等. 猴痘病原学及流行病学研究进展[J]. 中国病毒病杂志, 2022, 12(6):474-480.
[9]	World Health Organization. 2022-23 Mpox Outbreak: Global Trends[EB/OL]. [2023-09-13]. https://worldhealthorg.shinyapps.io/mpx_global/.
[10]	Kannan S, Shaik Syed Ali P, Sheeza A. Monkeypox: epidemiology, mode of transmission, clinical features, genetic clades and molecular properties[J]. Eur Rev Med Pharmacol Sci, 2022, 26(16):5983-5990.
[11]	Fine PE, Jezek Z, Grab B, et al. The transmission potential of monkeypox virus in human populations[J]. Int J Epidemiol, 1988, 17(3):643-650. pmid: 2850277
[12]	Luna N, Ramírez AL, Muñoz M, et al. Phylogenomic analysis of the monkeypox virus (MPXV) 2022 outbreak: emergence of a novel viral lineage?[J]. Travel Med Infect Dis,2022, 49:102402. doi: 10.1016/j.tmaid.2022.102402 URL
[13]	Chauhan RP, Fogel R, Limson J. Overview of diagnostic methods,disease prevalence and transmission of mpox (formerly monkeypox) in humans and animal reservoirs[J]. Microorganisms, 2023, 11(5):1186. doi: 10.3390/microorganisms11051186 URL
[14]	Petersen E, Zumla A, Hui DS, et al. Vaccination for monkeypox prevention in persons with high-risk sexual behaviours to control on-going outbreak of monkeypox virus clade 3[J]. Int J Infect Dis, 2022, 122:569-571. doi: 10.1016/j.ijid.2022.06.047 pmid: 35788415
[15]	祁贤. 猴痘病毒进化及检测技术研究进展[J]. 江苏预防医学, 2023, 34(1):1-7.
[16]	Li H, Zhang H, Ding K, et al. The evolving epidemiology of monkeypox virus[J]. Cytokine Growth Factor Rev, 2022, 68:1-12. doi: 10.1016/j.cytogfr.2022.10.002 URL
[17]	Karagoz A, Tombuloglu H, Alsaeed M, et al. Monkeypox (mpox) virus: classification, origin, transmission, genome organization, antiviral drugs, and molecular diagnosis[J]. J Infect Public Health, 2023, 16(4):531-541. doi: 10.1016/j.jiph.2023.02.003 URL
[18]	Isidro J, Borges V, Pinto M, et al. Phylogenomic characterization and signs of microevolution in the 2022 multi-country outbreak of monkeypox virus[J]. Nat Med, 2022, 28(8):1569-1572. doi: 10.1038/s41591-022-01907-y pmid: 35750157
[19]	Lopera JG, Falendysz EA, Rocke TE, et al. Attenuation of monkeypox virus by deletion of genomic regions[J]. Virology, 2015, 475:129-138. doi: 10.1016/j.virol.2014.11.009 pmid: 25462353
[20]	Li YJ, Hou JJ, Sun Z, et al. Monkeypox virus 2022, gene heterogeneity and protein polymorphism[J]. Signal Transduct Target Ther, 2023, 8(1):278.
[21]	Suleman M, Rashid F, Ali S, et al. Immunoinformatic-based design of immune-boosting multiepitope subunit vaccines against monkeypox virus and validation through molecular dynamics and immune simulation[J]. Front Immunol, 2022, 13:1042997. doi: 10.3389/fimmu.2022.1042997 URL
[22]	Szajner P, Jaffe H, Weisberg AS, et al. Vaccinia virus G7L protein Interacts with the A30L protein and is required for association of viral membranes with dense viroplasm to form immature virions[J]. J Virol, 2003, 77(6):3418-3429. pmid: 12610117
[23]	Rehm KE, Jones GJB, Tripp AA, et al. The poxvirus A35 protein is an immunoregulator[J]. J Virol, 2010, 84(1):418-425. doi: 10.1128/JVI.01802-09 pmid: 19828608
[24]	Shchelkunov SN, Totmenin AV, Safronov PF, et al. Analysis of the monkeypox virus genome[J]. Virology, 2002, 297(2):172-194. doi: 10.1006/viro.2002.1446 pmid: 12083817
[25]	O’Toole Á, Neher RA, Ndodo N, et al. APOBEC3 deaminase editing in mpox virus as evidence for sustained human transmission since at least 2016[J]. Science, 2023, 382(6670):595-600. doi: 10.1126/science.adg8116 pmid: 37917680
[26]	Gammon DB, Duraffour S, Rozelle DK, et al. A single vertebrate DNA virus protein disarms invertebrate immunity to RNA virus infection[J]. Elife, 2014, 3:e02910. doi: 10.7554/eLife.02910 URL
[27]	Keasey S, Pugh C, Tikhonov A, et al. Proteomic basis of the antibody response to monkeypox virus infection examined in cynomolgus macaques and a comparison to human smallpox vaccination[J]. PLoS One, 2010, 5(12):e15547. doi: 10.1371/journal.pone.0015547 URL
[28]	Maluquer de Motes C, Cooray S, Ren HW, et al. Inhibition of apoptosis and NF-κB activation by vaccinia protein N1 occur via distinct binding surfaces and make different contributions to virulence[J]. PLoS Pathog, 2011, 7(12):e1002430. doi: 10.1371/journal.ppat.1002430 URL
[29]	Spriggs MK, Hruby DE, Maliszewski CR, et al. Vaccinia and cowpox viruses encode a novel secreted interleukin-1-binding protein[J]. Cell, 1992, 71(1):145-152. pmid: 1339315
[30]	Estep RD, Messaoudi I, O’Connor MA, et al. Deletion of the monkeypox virus inhibitor of complement enzymes locus impacts the adaptive immune response to monkeypox virus in a nonhuman primate model of infection[J]. J Virol, 2011, 85(18):9527-9542. doi: 10.1128/JVI.00199-11 pmid: 21752919
[31]	Brennan G, Stoian AMM, Yu HB, et al. Molecular mechanisms of poxvirus evolution[J]. mBio, 2023, 14(1):e0152622. doi: 10.1128/mbio.01526-22 URL
[32]	Li H, Huang QZ, Zhang H, et al. The land-scape of immune response to monkeypox virus[J]. EBioMedicine, 2023, 87:104424. doi: 10.1016/j.ebiom.2022.104424 URL
[33]	Zhang K, Chen F, Shen HY, et al. Regulatory variants of APOBEC3 genes potentially associate with COVID-19 severity in populations with African ancestry. Sci Rep, 2023, 13(1):22435. doi: 10.1038/s41598-023-49791-x
[34]	Aljabali AA, Obeid MA, Nusair MB, et al. Monkeypox virus: an emerging epidemic[J]. Microb Pathog, 2022, 173(Pt A):105794.