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[4][5],以鼠類為宿主[6](也有感染狨的紀錄)[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 | |
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病毒分類 | |
(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
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異名 | |
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病毒學
仙台病毒具有包膜,包膜上具有血凝素-神經胺酸酶(HN)蛋白與融合蛋白(fusion protein,FN),前者兼具血球凝集素與神經胺酸酶的活性,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
仙台病毒的基因組為不分段的負鏈單股RNA,長約15,384nt,5′非轉譯區與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
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]與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(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]與SARS-CoV-2(復旦大學團隊)[37]的仙台病毒載體疫苗。
研究歷史
1952年,仙台市東北大學的研究人員M. Kuroya與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豬,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]。
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