仙台病毒

仙台病毒(Sendai virus,簡稱SeV)又稱鼠呼吸道病毒(murine respirovirus)、鼠副流感病毒一型(murine parainfluenza virus type 1)與日本凝血性病毒(hemagglutinating virus of Japan,HVJ),為副黏液病毒科呼吸道病毒屬的一種病毒[2][3],屬負鏈單股RNA病毒英语Negative-strand RNA virus[4][5],以鼠類為宿主[6](也有感染的紀錄)[7],不會感染人類與家畜。此病毒於1950年代在日本仙台市被發現,後來被用做病毒學研究的一種模式病毒

仙台病毒Infobox info icon2.svg
Image of Sendai virus.png
電子顯微鏡下的仙台病毒顆粒
病毒分類 e
–未分级– 病毒 Virus
域: 核糖病毒域 Riboviria
界: 正核糖病毒界 Orthornavirae
门: 負核糖病毒門 Negarnaviricota
纲: 單荊病毒綱 Monjiviricetes
目: 單股反鏈病毒目 Mononegavirales
科: 副黏液病毒科 Paramyxoviridae
属: 呼吸道病毒屬 Respirovirus
种: 仙台病毒 Murine respirovirus
異名
  • Sendai virus[1]

病毒學编辑

 
仙台病毒結構示意圖

仙台病毒具有包膜,包膜上具有血凝素-神經胺酸酶英语Hemagglutinin-neuraminidase(HN)蛋白與融合蛋白(fusion protein,FN),前者兼具血球凝集素神經胺酸酶的活性,可與宿主細胞結合並水解其表面的唾液酸以幫助感染[8][9];後者也是病毒感染宿主細胞所需的醣蛋白[10]。包膜內側的基質蛋白(M)有穩定包膜結構的功能[11]。病毒的核殼由基因組RNA與核殼蛋白(NP)[12]、磷蛋白(P)[13]、大蛋白(L)[14]及C蛋白組成[15],其中大蛋白為病毒RNA複製酶的活性亞基,磷蛋白亦為RNA複製酶的組成部分。

基因組编辑

 
仙台病毒的基因組與表現的的蛋白

仙台病毒的基因組為不分段的負鏈單股RNA,長約15,384nt5′非轉譯區3′非轉譯區分別長約50nt[5][16],共有6個編碼蛋白的基因,分別編碼核殼蛋白(NP)、磷蛋白(P)、基質蛋白(M)、融合蛋白(F)、血凝素-神經胺酸酶(HN)與大蛋白(L),基因排序為3′-NP-P-M-F-HN-L-5′[5][16]

編碼P蛋白的基因可以不同的開放閱讀框編碼其他蛋白質[5][17],此基因有5個起始密碼子,除編碼P蛋白外另外4個起始密碼子可編碼C、C'、Y1與Y2等4種蛋白(其中P、C、C'蛋白的開放閱讀框不同是渗漏扫描所致,Y1與Y2蛋白則是在轉譯起始時發生核糖體分流[18][19][17][20][21],此外P蛋白的信使核糖核酸轉錄時可能經RNA編輯而加入1或2個G而分別產生V蛋白與W蛋白[22],且其mRNA的末端可獨立轉譯出另一X蛋白[23]。這些由P蛋白基因衍生的蛋白皆為非結構蛋白,有協助感染宿主細胞、抑制宿主免疫反應等功能[22],其中C蛋白會少量表現於病毒的核殼上[15][24]

應用编辑

仙台病毒感染會使真核細胞融合成合胞體,因而被用於杂交瘤技术英语Hybridoma technology以量產單株抗體[25]。另外仙台病毒還在細胞實驗中被用作載體,將目標基因轉至細胞中,已被用於細胞螢光染色[26]、製造誘導性多能幹細胞(iPSC)[27][28]CRISPR[29]等技術,也可用於製作疫苗,目前已有研究團隊開發針對副流感病毒一型英语Human parainfluenza virus 1(HPV1)[30][31]人類免疫缺乏病毒[32]人類呼吸道合胞病毒(RSV)[33][34]結核病[35][36]SARS-CoV-2復旦大學團隊)[37]的仙台病毒載體疫苗。

研究歷史编辑

1952年,仙台市東北大學的研究人員M. Kuroya與石田名香雄日语石田名香雄嘗試從一名患肺炎逝世的嬰兒肺樣本中分離病原,將分離的病原轉至小鼠中[38][39]。但1954年國立保健醫療科學院日语國立保健醫療科學院的學者提出另一假說,認為實驗中使用的小鼠可能原本即感染病毒,而非來自病人樣本,並將此病毒分離、命名為仙台病毒[40],此理論後來受到許多實驗結果支持[5],因此歷史緣由,仙台病毒曾一度被認為是感染人類的病毒[41][42]。另外因1950年代日本豬流感疫情中,許多豬隻體內被發現有抗仙台病毒的抗體,過去還認為仙台病毒可感染,但後續研究顯示這些豬隻應為被豬副流感病毒(porcine parainfluenza)等其他類似病毒感染[30][41][43]

參考文獻编辑

  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 .