维基百科

仙台病毒

仙台病毒（Sendai virus，简称SeV）又称鼠呼吸道病毒（murine respirovirus）、鼠副流感病毒一型（murine parainfluenza virus type 1）与日本凝血性病毒（hemagglutinating virus of Japan，HVJ），为副黏液病毒科呼吸道病毒属的一种病毒[2][3]，属负链单股RNA病毒（英语：Negative-strand RNA virus）[4][5]，以鼠类为宿主[6]（也有感染狨的纪录）[7]，不会感染人类与家畜。此病毒于1950年代在日本仙台市被发现，后来被用做病毒学研究的一种模式病毒。

仙台病毒
病毒分类 编辑
（未分级）： 病毒 Virus
域： 核糖病毒域 Riboviria
界： 正核糖病毒界 Orthornavirae
门： 负核糖病毒门 Negarnaviricota
纲： 单荆病毒纲 Monjiviricetes
目： 单股反链病毒目 Mononegavirales
科： 副黏液病毒科 Paramyxoviridae
属： 呼吸道病毒属 Respirovirus
种：
仙台病毒 Murine respirovirus
异名
  • Sendai virus[1]

病毒学

 
仙台病毒结构示意图

仙台病毒具有包膜，包膜上具有血凝素-神经胺酸酶（英语：Hemagglutinin-neuraminidase）（HN）蛋白与融合蛋白（fusion protein，FN），前者兼具血球凝集素与神经胺酸酶的活性，可与宿主细胞结合并水解其表面的唾液酸以帮助感染[8][9]；后者也是病毒感染宿主细胞所需的糖蛋白[10]。包膜内侧的基质蛋白（M）有稳定包膜结构的功能[11]。病毒的核壳由基因组RNA与核壳蛋白（NP）[12]、磷蛋白（P）[13]、大蛋白（L）[14]及C蛋白组成[15]，其中大蛋白为病毒RNA复制酶的活性亚基，磷蛋白亦为RNA复制酶的组成部分。

基因组

 
仙台病毒的基因组与表现的的蛋白

仙台病毒的基因组为不分段的负链单股RNA，长约15,384nt，5′非转译区与3′非转译区分别长约50nt[5][16]，共有6个编码蛋白的基因，分别编码核壳蛋白（NP）、磷蛋白（P）、基质蛋白（M）、融合蛋白（F）、血凝素-神经胺酸酶（HN）与大蛋白（L），基因排序为3′-NP-P-M-F-HN-L-5′[5][16]。

编码P蛋白的基因可以不同的开放阅读框编码其他蛋白质[5][17]，此基因有5个起始密码子，除编码P蛋白外另外4个起始密码子可编码C、C'、Y1与Y2等4种蛋白（其中P、C、C'蛋白的开放阅读框不同是渗漏扫描所致，Y1与Y2蛋白则是在转译起始时发生核糖体分流[18][19]）[17][20][21]，此外P蛋白的信使核糖核酸转录时可能经RNA编辑而加入1或2个G而分别产生V蛋白与W蛋白[22]，且其mRNA的末端可独立转译出另一X蛋白[23]。这些由P蛋白基因衍生的蛋白皆为非结构蛋白，有协助感染宿主细胞、抑制宿主免疫反应等功能[22]，其中C蛋白会少量表现于病毒的核壳上[15][24]。

应用

仙台病毒感染会使真核细胞融合成合胞体，因而被用于杂交瘤技术（英语：Hybridoma technology）以量产单克隆抗体[25]。另外仙台病毒还在细胞实验中被用作载体，将目标基因转至细胞中，已被用于细胞萤光染色[26]、制造诱导性多能干细胞（iPSC）[27][28]与CRISPR[29]等技术，也可用于制作疫苗，目前已有研究团队开发针对副流感病毒一型（英语：Human parainfluenza virus 1）（HPV1）[30][31]、人类免疫缺乏病毒[32]、人类呼吸道合胞病毒（RSV）[33][34]、结核病[35][36]与SARS-CoV-2（复旦大学团队）[37]的仙台病毒载体疫苗。

研究历史

1952年，仙台市东北大学的研究人员M. Kuroya与石田名香雄（日语：石田名香雄）尝试从一名患肺炎逝世的婴儿肺样本中分离病原，将分离的病原转至小鼠中[38][39]。但1954年国立保健医疗科学院（日语：國立保健醫療科學院）的学者提出另一假说，认为实验中使用的小鼠可能原本即感染病毒，而非来自病人样本，并将此病毒分离、命名为仙台病毒[40]，此理论后来受到许多实验结果支持[5]，因此历史缘由，仙台病毒曾一度被认为是感染人类的病毒[41][42]。另外因1950年代日本猪流感疫情中，许多猪只体内被发现有抗仙台病毒的抗体，过去还认为仙台病毒可感染猪，但后续研究显示这些猪只应为被猪副流感病毒（porcine parainfluenza）等其他类似病毒感染[30][41][43]。

参考文献

  1. ^ Walker, Peter. Implementation of taxon-wide non-Latinized binomial species names in the family Rhabdoviridae (PDF). International Committee on Taxonomy of Viruses (ICTV): 7. 2015-06-15 [2019-02-06]. （原始内容 (PDF)存档于2021-12-04）. 
  2. ^ Taxonomy - Respirovirus. UniProt. [2021-12-04]. （原始内容存档于2022-04-17）. 
  3. ^ Respirovirus. ViralZone. [2021-12-04]. （原始内容存档于2022-02-09）. 
  4. ^ Paramyxoviridae. UniProt. [2021-12-04]. （原始内容存档于2022-04-17）. 
  5. ^ 5.0 5.1 5.2 5.3 5.4 Faísca P, Desmecht D. Sendai virus, the mouse parainfluenza type 1: a longstanding pathogen that remains up-to-date. Research in Veterinary Science. February 2007, 82 (1): 115–25. PMID 16759680. doi:10.1016/j.rvsc.2006.03.009. 
  6. ^ MacLachlan, N. James; Dubovi, Edward J. (编). Chapter 17 - Paramyxoviridae and Pneumoviridae. Fenner's Veterinary Virology Fifth. Academic Press. 2017: 327–356. ISBN 9780128009468. S2CID 214757272. doi:10.1016/B978-0-12-800946-8.00017-9. 
  7. ^ Flecknell PA, Parry R, Needham JR, Ridley RM, Baker HF, Bowes P. Respiratory disease associated with parainfluenza Type I (Sendai) virus in a colony of marmosets (Callithrix jacchus). Laboratory Animals. April 1983, 17 (2): 111–3. PMID 6306336. S2CID 7413539. doi:10.1258/002367783780959448. 
  8. ^ HN - Hemagglutinin-neuraminidase - Sendai virus (strain Z) (SeV) - HN gene & protein. www.uniprot.org. [2019-08-09]. （原始内容存档于2021-12-04）. 
  9. ^ Scheid A, Choppin PW. Identification of biological activities of paramyxovirus glycoproteins. Activation of cell fusion, hemolysis, and infectivity of proteolytic cleavage of an inactive precursor protein of Sendai virus. Virology. February 1974, 57 (2): 475–90. PMID 4361457. doi:10.1016/0042-6822(74)90187-1. 
  10. ^ F - Fusion glycoprotein F0 precursor - Sendai virus (strain Z) (SeV) - F gene & protein. www.uniprot.org. [2019-08-09]. （原始内容存档于2022-05-09）. 
  11. ^ M - Matrix protein - Sendai virus (strain Ohita) (SeV) - M gene & protein. www.uniprot.org. [2019-08-09]. （原始内容存档于2022-05-09）. 
  12. ^ N - Nucleoprotein - Sendai virus (strain Z) (SeV) - N gene & protein. www.uniprot.org. [2019-08-09]. （原始内容存档于2022-05-09）. 
  13. ^ P/V/C - Phosphoprotein - Sendai virus (strain Harris) (SeV) - P/V/C gene & protein. www.uniprot.org. [2019-08-09]. （原始内容存档于2022-05-09）. 
  14. ^ L - RNA-directed RNA polymerase L - Sendai virus (strain Enders) (SeV) - L gene & protein. www.uniprot.org. [2019-08-09]. （原始内容存档于2022-04-12）. 
  15. ^ 15.0 15.1 Yamada H, Hayata S, Omata-Yamada T, Taira H, Mizumoto K, Iwasaki K. Association of the Sendai virus C protein with nucleocapsids. Archives of Virology. 1990, 113 (3–4): 245–53. PMID 2171459. S2CID 24592567. doi:10.1007/bf01316677. 
  16. ^ 16.0 16.1 Sakai Y, Kiyotani K, Fukumura M, Asakawa M, Kato A, Shioda T, et al. Accommodation of foreign genes into the Sendai virus genome: sizes of inserted genes and viral replication. FEBS Letters. August 1999, 456 (2): 221–6. PMID 10456313. S2CID 1285541. doi:10.1016/s0014-5793(99)00960-6. 
  17. ^ 17.0 17.1 Curran J, Kolakofsky D. Ribosomal initiation from an ACG codon in the Sendai virus P/C mRNA. The EMBO Journal. January 1988, 7 (1): 245–51. PMC 454264  . PMID 2834203. doi:10.1002/j.1460-2075.1988.tb02806.x. 
  18. ^ De Breyne, S; Simonet, V; Pelet, T; Curran, J. Identification of a cis-acting element required for shunt-mediated translational initiation of the Sendai virus Y proteins. Nucleic Acids Research. 2003, 31 (2): 608–18. PMC 140508  . PMID 12527769. doi:10.1093/nar/gkg143. 
  19. ^ Latorre, P; Kolakofsky, D; Curran, J. Sendai virus Y proteins are initiated by a ribosomal shunt. Molecular and Cellular Biology. 1998, 18 (9): 5021–31. PMC 109087  . PMID 9710586. doi:10.1128/mcb.18.9.5021. 
  20. ^ Dillon PJ, Gupta KC. Expression of five proteins from the Sendai virus P/C mRNA in infected cells. Journal of Virology. February 1989, 63 (2): 974–7. PMC 247778  . PMID 2536120. doi:10.1128/JVI.63.2.974-977.1989. 
  21. ^ de Breyne S, Simonet V, Pelet T, Curran J. Identification of a cis-acting element required for shunt-mediated translational initiation of the Sendai virus Y proteins. Nucleic Acids Research. January 2003, 31 (2): 608–18. PMC 140508  . PMID 12527769. doi:10.1093/nar/gkg143. 
  22. ^ 22.0 22.1 Garcin D, Curran J, Itoh M, Kolakofsky D. Longer and shorter forms of Sendai virus C proteins play different roles in modulating the cellular antiviral response. Journal of Virology. August 2001, 75 (15): 6800–7. PMC 114406  . PMID 11435558. doi:10.1128/JVI.75.15.6800-6807.2001. 
  23. ^ Curran J, Kolakofsky D. Scanning independent ribosomal initiation of the Sendai virus X protein. The EMBO Journal. September 1988, 7 (9): 2869–74. PMC 457080  . PMID 2846286. doi:10.1002/j.1460-2075.1988.tb03143.x. 
  24. ^ Irie T, Nagata N, Yoshida T, Sakaguchi T. Recruitment of Alix/AIP1 to the plasma membrane by Sendai virus C protein facilitates budding of virus-like particles. Virology. February 2008, 371 (1): 108–20. PMID 18028977. doi:10.1016/j.virol.2007.09.020. 
  25. ^ Köhler G, Milstein C. Continuous cultures of fused cells secreting antibody of predefined specificity. Nature. August 1975, 256 (5517): 495–7. Bibcode:1975Natur.256..495K. PMID 1172191. S2CID 4161444. doi:10.1038/256495a0. 
  26. ^ Agungpriyono DR, Yamaguchi R, Uchida K, Tohya Y, Kato A, Nagai Y, et al. Green fluorescent protein gene insertion of Sendai Virus infection in nude mice: possibility as an infection tracer. The Journal of Veterinary Medical Science. February 2000, 62 (2): 223–8. PMID 10720198. doi:10.1292/jvms.62.223  . 
  27. ^ Fusaki N, Ban H, Nishiyama A, Saeki K, Hasegawa M. Efficient induction of transgene-free human pluripotent stem cells using a vector based on Sendai virus, an RNA virus that does not integrate into the host genome. Proceedings of the Japan Academy. Series B, Physical and Biological Sciences. 2009, 85 (8): 348–62. Bibcode:2009PJAB...85..348F. PMC 3621571  . PMID 19838014. doi:10.2183/pjab.85.348. 
  28. ^ Ban H, Nishishita N, Fusaki N, Tabata T, Saeki K, Shikamura M, et al. Efficient generation of transgene-free human induced pluripotent stem cells (iPSCs) by temperature-sensitive Sendai virus vectors. Proceedings of the National Academy of Sciences of the United States of America. August 2011, 108 (34): 14234–9. Bibcode:2011PNAS..10814234B. PMC 3161531  . PMID 21821793. doi:10.1073/pnas.1103509108  . 
  29. ^ Park A, Hong P, Won ST, Thibault PA, Vigant F, Oguntuyo KY, et al. Sendai virus, an RNA virus with no risk of genomic integration, delivers CRISPR/Cas9 for efficient gene editing. Molecular Therapy: Methods & Clinical Development. 2016-08-24, 3: 16057. PMC 4996130  . PMID 27606350. doi:10.1038/mtm.2016.57. 
  30. ^ 30.0 30.1 Slobod KS, Shenep JL, Luján-Zilbermann J, Allison K, Brown B, Scroggs RA, et al. Safety and immunogenicity of intranasal murine parainfluenza virus type 1 (Sendai virus) in healthy human adults. Vaccine. August 2004, 22 (23–24): 3182–6. PMID 15297072. doi:10.1016/j.vaccine.2004.01.053. 
  31. ^ Adderson E, Branum K, Sealy RE, Jones BG, Surman SL, Penkert R, et al. Safety and immunogenicity of an intranasal Sendai virus-based human parainfluenza virus type 1 vaccine in 3- to 6-year-old children. Clinical and Vaccine Immunology. March 2015, 22 (3): 298–303. PMC 4340902  . PMID 25552633. doi:10.1128/CVI.00618-14. 
  32. ^ Seki, Sayuri; Matano, Tetsuro. Development of a Sendai virus vector-based AIDS vaccine inducing T cell responses. Expert Review of Vaccines. 2015-10-29, 15 (1): 119–127. ISSN 1476-0584. PMID 26512881. S2CID 27197590. doi:10.1586/14760584.2016.1105747. 
  33. ^ Russell CJ, Hurwitz JL. Sendai virus as a backbone for vaccines against RSV and other human paramyxoviruses. Expert Review of Vaccines. 2015-12-09, 15 (2): 189–200. PMC 4957581  . PMID 26648515. doi:10.1586/14760584.2016.1114418. 
  34. ^ Jones BG, Sealy RE, Rudraraju R, Traina-Dorge VL, Finneyfrock B, Cook A, et al. Sendai virus-based RSV vaccine protects African green monkeys from RSV infection. Vaccine. January 2012, 30 (5): 959–68. PMC 3256274  . PMID 22119594. doi:10.1016/j.vaccine.2011.11.046. 
  35. ^ Hu Z, Wong KW, Zhao HM, Wen HL, Ji P, Ma H, et al. Sendai Virus Mucosal Vaccination Establishes Lung-Resident Memory CD8T Cell Immunity and Boosts BCG-Primed Protection against TB in Mice. Molecular Therapy. May 2017, 25 (5): 1222–1233. PMC 5417795  . PMID 28342639. doi:10.1016/j.ymthe.2017.02.018. 
  36. ^ Hu Z, Jiang W, Gu L, Qiao D, Shu T, Lowrie DB, et al. Heterologous prime-boost vaccination against tuberculosis with recombinant Sendai virus and DNA vaccines. Journal of Molecular Medicine. December 2019, 97 (12): 1685–1694. PMID 31786669. S2CID 208359634. doi:10.1007/s00109-019-01844-3  . 
  37. ^ Carey, Karen. Increasing number of biopharma drugs target COVID-19 as virus spreads. BioWorld. 2020-03-05 [2021-12-04]. （原始内容存档于2020-02-27）. 
  38. ^ Kuroya M, Ishida N. Newborn virus pneumonitis (type Sendai). II. The isolation of a new virus possessing hemagglutinin activity. Yokohama Medical Bulletin. August 1953, 4 (4): 217–33. PMID 13137076. 
  39. ^ Kuroya M, Ishida N, Shiratori T. Newborn virus pneumonitis (type Sendai). II. The isolation of a new virus. The Tohoku Journal of Experimental Medicine. June 1953, 58 (1): 62. PMID 13102529. doi:10.1620/tjem.58.62  . 
  40. ^ Fukumi H, Nishikawa F, Kitayama T. A pneumotropic virus from mice causing hemagglutination. Japanese Journal of Medical Science & Biology. August 1954, 7 (4): 345–63. PMID 13232830. doi:10.7883/yoken1952.7.345  . 
  41. ^ 41.0 41.1 Ishida N, Homma M. Sendai virus. Advances in Virus Research. 1978, 23: 349–83. ISBN 9780120398232. PMID 219669. doi:10.1016/S0065-3527(08)60103-7. 
  42. ^ Sendai virus infectious agent. Encyclopedia Britannica. [2019-08-26]. （原始内容存档于2021-12-04）. 
  43. ^ Lau SK, Woo PC, Wu Y, Wong AY, Wong BH, Lau CC, et al. Identification and characterization of a novel paramyxovirus, porcine parainfluenza virus 1, from deceased pigs. The Journal of General Virology. October 2013, 94 (Pt 10): 2184–90. PMID 23918408. doi:10.1099/vir.0.052985-0  . 
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