魏建春，安靜

首都醫(yī)科大學(xué)病原生物學(xué)教研室，北京 100069

·綜述·

微小RNA在病毒與宿主相互作用中的功能

魏建春，安靜

首都醫(yī)科大學(xué)病原生物學(xué)教研室，北京 100069

微小RNA(microRNA，miRNA)是一類長(zhǎng)度為22個(gè)核苷酸左右的內(nèi)源性非編碼小RNA分子。自1993年最先從秀麗隱桿線蟲體內(nèi)發(fā)現(xiàn)miRNA以來，目前為止已有35 000多條miRNA在植物、動(dòng)物及病毒中被發(fā)現(xiàn)。它們作為重要的轉(zhuǎn)錄調(diào)控因子，參與細(xì)胞分化、凋亡、代謝、信號(hào)轉(zhuǎn)導(dǎo)、免疫等多種生物學(xué)過程。病毒和宿主細(xì)胞均可編碼miRNA，病毒編碼的miRNA可改變宿主內(nèi)環(huán)境，而宿主編碼的miRNA則可影響病毒生存。本文就miRNA對(duì)病毒與宿主相互作用的調(diào)控進(jìn)行綜述。

微小RNA；皰疹病毒；腫瘤；病毒-宿主相互作用

1 微小RNA

微小RNA(microRNA，miRNA)是一類長(zhǎng)度為22個(gè)核苷酸(nucleotide，nt)左右的內(nèi)源性非編碼小RNA分子，在動(dòng)植物體內(nèi)發(fā)揮重要的生物學(xué)作用[1-2]。最早揭開miRNA序幕的是哈佛大學(xué)的Lee等，他們?cè)?993年指出lin-4基因可編碼一段22 nt的RNA片段，通過調(diào)控靶基因lin-14而控制秀麗隱桿線蟲的發(fā)育時(shí)序[3]。7年后，Reinhart等報(bào)道let-7可編碼長(zhǎng)度為21 nt的RNA片段，通過與靶基因的3′非編碼區(qū)(3′-untranslated region，3′-UTR)相結(jié)合，控制秀麗隱桿線蟲從幼蟲到成蟲的轉(zhuǎn)變[4]。隨著檢測(cè)技術(shù)的不斷提高，人們發(fā)現(xiàn)不僅在線蟲，果蠅、魚和哺乳動(dòng)物等均有miRNA存在，從而開啟了miRNA研究的熱潮[5-7]。miRBase數(shù)據(jù)庫(kù)(www.mirbase.org)統(tǒng)計(jì)顯示，目前已發(fā)現(xiàn)的miRNA在223個(gè)物種中存在，共有發(fā)夾前體miRNA(pre-miRNA)28 645條，成熟miRNA序列35 828條。在人等脊椎動(dòng)物中，miRNA分布于胚胎、造血干細(xì)胞、肝臟、心臟、腦等多種組織和細(xì)胞中。

miRNA的轉(zhuǎn)錄單位通常是一段獨(dú)立的基因，可位于編碼蛋白基因的內(nèi)含子中，也可位于外顯子中[8]。經(jīng)典理論認(rèn)為，miRNA的生物學(xué)發(fā)生首先由轉(zhuǎn)錄單位在細(xì)胞核中被RNA聚合酶Ⅱ轉(zhuǎn)錄為原始miRNA(primary miRNA，pri-miRNA)，其長(zhǎng)度較長(zhǎng)，可超過1 kb。其后在核酸酶Drosha及其輔助因子Pasha作用下，pri-miRNA被剪切成60～70 nt的發(fā)夾結(jié)構(gòu)，形成pre-miRNA。這些pre-miRNA由Exportin-5輸送至細(xì)胞質(zhì)中，進(jìn)一步被Dicer(RNase Ⅲ家族)剪切，形成約22 bp的雙鏈RNA復(fù)合體。經(jīng)解螺旋酶作用后，5′端具有低穩(wěn)定性的引導(dǎo)鏈被優(yōu)先選擇，與細(xì)胞質(zhì)中的Ago等蛋白結(jié)合，形成RNA誘導(dǎo)的沉默復(fù)合體(RNA-induced silencing complex，RISC)[2,9]。在RISC中，miRNA發(fā)育成熟，參與基因轉(zhuǎn)錄后調(diào)節(jié)。調(diào)節(jié)機(jī)制一般有兩種，即靶向識(shí)別降解和轉(zhuǎn)錄抑制。前者主要存在于植物中，后者則多見于動(dòng)物中。miRNA通過“種子區(qū)”(seed region；第2～7位堿基)與靶mRNA的3′-UTR互補(bǔ)結(jié)合，進(jìn)而影響基因的表達(dá)[10]。近幾年研究顯示，miRNA在動(dòng)物中不僅可引起mRNA轉(zhuǎn)錄抑制，有些miRNA還可促進(jìn)靶基因轉(zhuǎn)錄[11-12]。

miRNA在染色體上是非隨機(jī)分布的，許多miRNA基因緊密連接，成簇排列[13-14]。成簇排列的miRNA即使序列不同，調(diào)節(jié)功能仍可相似。這種基因簇排列方式提示miRNA有復(fù)雜的調(diào)控機(jī)制。此外，miRNA在不同物種之間高度保守，這種保守性不僅體現(xiàn)在序列上，在二級(jí)結(jié)構(gòu)中也有所表現(xiàn)。同源性越近，miRNA之間保守性越明顯[15-17]。

miRNA在表達(dá)上有幾個(gè)明顯特征。首先，其具有明顯的細(xì)胞和組織特異性[18]。2005年Wienholds等研究發(fā)現(xiàn)，斑馬魚(zebrafish)體內(nèi)多數(shù)(68%)miRNA均有組織學(xué)特異性，推測(cè)miRNA參與組織的分化和特征維持[19]。在其他動(dòng)物中也觀察到相似現(xiàn)象，如miR-1主要在心臟中表達(dá)[7]，miR-122主要在肝臟中表達(dá)[20]，miR-223主要在造血系統(tǒng)中表達(dá)等[21]。其次，miRNA的表達(dá)具有時(shí)序性。miR-35-miR-41基因簇只在秀麗隱桿線蟲胚胎和幼蟲期表達(dá)[6]；miR-290-miR-295僅存在于小鼠胚胎干細(xì)胞，在其他發(fā)育階段并沒有發(fā)現(xiàn)[22]。由此推測(cè)，在生物不同發(fā)展階段miRNA有其特定的表達(dá)模式。最后，細(xì)胞中不同miRNA表達(dá)量可非常高或非常低。Lim等在研究秀麗隱桿線蟲時(shí)發(fā)現(xiàn)，每個(gè)細(xì)胞中miR-2、miR-52、miR-58可表達(dá)50 000個(gè)分子，甚至高于U6的表達(dá)量；而miR-124低表達(dá)，每個(gè)細(xì)胞中只有800個(gè)[23]。造成這種差異的機(jī)制有待進(jìn)一步研究。

隨著miRNA研究的深入及其發(fā)現(xiàn)數(shù)量越來越多，人們對(duì)miRNA關(guān)注的焦點(diǎn)逐漸轉(zhuǎn)向作用機(jī)制，尤其是與人類疾病相關(guān)方面[24-25]?，F(xiàn)已證明miRNA在細(xì)胞分化和凋亡、代謝、信號(hào)轉(zhuǎn)導(dǎo)、免疫和移形等方面均扮演著重要角色，其表達(dá)異常與腫瘤、病毒感染、免疫性疾病、神經(jīng)退行性病變等疾病密切相關(guān)。在病毒感染過程中，miRNA作為關(guān)鍵效應(yīng)分子，在宿主-抗原相互作用中發(fā)揮重要功能。病毒和宿主均可編碼miRNA，病毒編碼的miRNA有助于病毒實(shí)現(xiàn)免疫逃逸，而宿主編碼的miRNA則對(duì)病毒感染有促進(jìn)或抑制作用。

2 病毒miRNA

miRNA可由病毒編碼而來，主要集中于皰疹病毒科、多瘤病毒科和反轉(zhuǎn)錄病毒科。這些可編碼miRNA的病毒絕大多數(shù)是雙鏈DNA(double-stranded DNA，dsDNA)病毒[26-28]。除少數(shù)幾種病毒〔鼠皰疹病毒(murine herpesvirus，MHV)、腺病毒和卡波西肉瘤相關(guān)皰疹病毒(Kaposi’s sarcoma-associated herpesvirus，KSHV)〕外，大多數(shù)病毒編碼miRNA的過程與真核細(xì)胞類似，由轉(zhuǎn)錄單位或內(nèi)含子通過RNA聚合酶Ⅱ轉(zhuǎn)錄而來。不同的是，病毒編碼的miRNA分子之間同源性并不明顯[26]。

2.1 皰疹病毒科

皰疹病毒根據(jù)理化性質(zhì)不同分為α、β和γ 3個(gè)亞科，包括α亞科的單純皰疹病毒(herpes simplex virus，HSV)1型和2型，β亞科的人巨細(xì)胞病毒(human cytomegalovirus，HCMV)和γ亞科的人EB病毒(Epstein-Barr virus，EBV)、KSHV及MHV68[29]，可導(dǎo)致從輕微感染至癌癥形成等多種病變。

皰疹病毒是病毒編碼miRNA的主要來源。HSV分為HSV-1和HSV-2兩個(gè)亞型，一般經(jīng)呼吸道、生殖器黏膜及破損皮膚進(jìn)入體內(nèi)而潛伏感染，是最早發(fā)現(xiàn)的人類皰疹病毒。測(cè)序發(fā)現(xiàn)，人和小鼠HSV-1可編碼7種miRNA，其中6種局限于非編碼潛伏相關(guān)轉(zhuǎn)錄子(latency-associated transcript，LAT)中，另一種(miR-H1)則可在進(jìn)行復(fù)制的細(xì)胞中表達(dá)。這些miRNA參與病毒潛伏狀態(tài)維持及避免遭受機(jī)體免疫系統(tǒng)清除[30-31]。HSV-2編碼的miRNA有5種，均局限于LAT中[32-33]。HCMV在人群中感染非常普遍，但大多表現(xiàn)為隱性感染。不同于HSV，HCMV編碼的miRNA分散排列在整個(gè)基因組中，這些miRNA在細(xì)胞復(fù)制的早期出現(xiàn)，提示可能參與細(xì)胞周期的調(diào)節(jié)。有研究指出，HCMV可通過編碼miR-UL112下調(diào)主要組織相容性復(fù)合體(major histocompatibility complex，MHC)Ⅰ類鏈相關(guān)蛋白B的表達(dá)，減少其與自然殺傷(natural killer，NK)細(xì)胞活化性受體NKG2D結(jié)合，降低NK細(xì)胞對(duì)HCMV的殺傷效應(yīng)[34-35]。EBV與鼻咽癌(nasopharyngeal carcinoma，NPC)、Burkitt淋巴瘤(Burkitt lymphoma，BL)、胃癌(gastric cancer，GC)等多種腫瘤的發(fā)生有關(guān)。病毒可編碼miRNA的現(xiàn)象，最早于研究RNA干擾EBV感染人B細(xì)胞過程中發(fā)現(xiàn)[36]。已知EBV可編碼至少25種miRNA，分為BHRF1和BART兩組。BHRF1組miRNA選擇性高表達(dá)于EBV 3期潛伏感染細(xì)胞中，如淋巴母細(xì)胞(lymphoblastoid cell line，LCL)和BL等B細(xì)胞中；在1期或2期潛伏感染階段(如NPC)的細(xì)胞中檢測(cè)不到。BART組miRNA在病毒潛伏感染的B細(xì)胞中也可檢測(cè)到，但主要高表達(dá)于2期潛伏感染的NPC上皮細(xì)胞中。由此推測(cè)，miRNA可能參與EBV感染過程中靶細(xì)胞的轉(zhuǎn)移和分化[37]。KSHV可引起卡波西肉瘤、原發(fā)性滲出性淋巴瘤(primary exudative lymphoma，PEL)等病變。目前發(fā)現(xiàn)KSHV可編碼12條miRNA，編碼基因主要位于非編碼區(qū)長(zhǎng)度約4.5 kb的v-cyclin與K12/Kaposin之間。其中miR-K1-K9及miR-K11位于ORF71與kaposirr之間，剩余兩條則分別位于基因組編碼區(qū)(miR-K10)和KSHVK12基因3′-UTR區(qū)(miR-K12)。研究發(fā)現(xiàn)，miR-K10、miR-K12與另外10種miRNA在病毒裂解性復(fù)制過程中表達(dá)水平不同，推測(cè)它們?cè)诓《静煌芷谒鸬淖饔貌煌唧w機(jī)制有待研究[29]。計(jì)算機(jī)預(yù)測(cè)發(fā)現(xiàn)，miRNA可能的靶基因中包括多種KSHV感染相關(guān)的mRNA，提示它們可能還參與細(xì)胞凋亡、信號(hào)轉(zhuǎn)導(dǎo)、B細(xì)胞調(diào)控等多種生物學(xué)過程[38]。MHV68不僅能感染實(shí)驗(yàn)小鼠，還能在體外感染多B細(xì)胞系、骨髓細(xì)胞系及哺乳動(dòng)物的成纖維細(xì)胞和上皮細(xì)胞等。Pfeffer等研究發(fā)現(xiàn)，MHV68可編碼至少9種miRNA，由RNA聚合酶Ⅲ轉(zhuǎn)錄而來，成簇聚集在病毒線性基因組M1蛋白編碼區(qū)[39]。這些結(jié)果提示，miRNA的轉(zhuǎn)錄可能存在多種方式[36]。

2.2 多瘤病毒科

多瘤病毒科因其能誘導(dǎo)機(jī)體產(chǎn)生多種腫瘤而得名，包括猴空泡病毒40 (simian vacuolating virus 40或simian virus 40，SV40)、鼠多瘤病毒(murine polyomavirus)、人多瘤病毒(多瘤病毒、JC多瘤病毒)等。最具代表性的為SV40。研究發(fā)現(xiàn)，SV40在感染后期可編碼miR-S1。不同于皰疹病毒來源的miRNA，miR-S1是第1個(gè)作用靶點(diǎn)明確的miRNA[40]。miR-S1并不影響病毒復(fù)制，其與病毒感染早期產(chǎn)生的靶mRNA幾乎完全互補(bǔ)結(jié)合使之被清除，從而降低病毒T抗原表達(dá)。該過程有助于病毒偽裝，逃脫宿主特異性細(xì)胞毒性T細(xì)胞(cytotoxic T lymphocyte，CTL)識(shí)別、殺傷、破壞病毒感染細(xì)胞等免疫反應(yīng)。研究多瘤病毒時(shí)也發(fā)現(xiàn)，miRNA可與靶mRNA結(jié)合，降低病毒抗原表達(dá)，逃逸宿主免疫反應(yīng)[41]。

2.3 反轉(zhuǎn)錄病毒科

反轉(zhuǎn)錄病毒是一種有包膜的RNA病毒。目前關(guān)于RNA病毒編碼miRNA的研究仍處于起步階段。人類免疫缺陷病毒1型(human immunodeficiency virus type 1，HIV-1)屬慢病毒亞科，可編碼長(zhǎng)度約50 nt的反式激活效應(yīng)元件(trans-activation responsive element，TAR)片段。Klase等用生物素標(biāo)記證實(shí)TAR可被細(xì)胞Dicer酶剪切，形成病毒miRNA[42]。Ouellet等也通過實(shí)驗(yàn)證實(shí)TAR是病毒miRNA的來源[43]。人們推測(cè)HIV-1編碼的miRNA可能通過改變宿主T細(xì)胞、巨噬細(xì)胞和樹突細(xì)胞活性，阻斷CD28、CD4和其他一些細(xì)胞因子產(chǎn)生，從而幫助HIV建立和維持潛伏感染及再激發(fā)的過程[44-45]。

2.4 其他

腺病毒是無包膜的dsDNA病毒，可感染機(jī)體多臟器，如呼吸道、胃腸道、肝臟和眼等。腺病毒感染宿主后，可產(chǎn)生長(zhǎng)度約160 nt富含CG的RNA聚合酶Ⅲ轉(zhuǎn)錄產(chǎn)物[46-47]。其結(jié)構(gòu)類似于pre-miRNA，可在不需病毒復(fù)制和蛋白表達(dá)的條件下被輸送至細(xì)胞質(zhì)中剪切為小病毒相關(guān)RNA分子(small virus-associated RNA，svaRNA)。在RISC中svaRNA與Argonaute 2結(jié)合，抑制其互補(bǔ)序列的表達(dá)。若該過程被阻斷，腺病毒的感染效率降低，提示svaRNA 參與腺病毒感染[48]。目前尚未證實(shí)其他病毒有編碼病毒miRNA的能力[29]，但隨著技術(shù)進(jìn)步，相信會(huì)有更多可編碼miRNA的病毒被發(fā)現(xiàn)。

3 宿主miRNA

宿主編碼的miRNA除調(diào)節(jié)功能外，還有抗病毒作用。哺乳類動(dòng)物中這一作用的研究還處于起步階段。Lecellier等研究發(fā)現(xiàn)，哺乳類動(dòng)物細(xì)胞可通過編碼miR-32抑制靈長(zhǎng)類泡沫病毒1 型(primate foamy virus 1，PFV-1)的聚集[49]。Triboulet等則發(fā)現(xiàn)細(xì)胞編碼miRNA可抑制HIV復(fù)制[50]。宿主感染病毒后，宿主miRNA表達(dá)會(huì)發(fā)生很大變化。盡管這種變化的發(fā)生機(jī)制尚不清楚，但可以肯定宿主編碼miRNA與病毒所致疾病密切相關(guān)[29,51-53]。

3.1 宿主miRNA與腫瘤

EBV潛伏膜蛋白1(latent membrane protein 1，LMP1)可阻斷正常信號(hào)轉(zhuǎn)導(dǎo)通路〔如核因子κB(nuclear factor κB，NF-κB)、活化蛋白1(activator protein 1，AP-1)〕，調(diào)控細(xì)胞的生長(zhǎng)周期，在EBV相關(guān)疾病尤其是惡性腫瘤的發(fā)展、侵襲中起重要作用。Cameron等研究發(fā)現(xiàn)，在EBV潛伏感染細(xì)胞中，LMP1可通過誘導(dǎo)miR-146a基因啟動(dòng)子區(qū)的兩個(gè)NF-κB結(jié)合位點(diǎn)，使其表達(dá)上調(diào)[54]；miR-146a異常表達(dá)會(huì)導(dǎo)致腫瘤發(fā)生[55-57]。Anastasiadou等研究發(fā)現(xiàn)，EBV感染BL細(xì)胞系過程中，LMP1可通過C端兩個(gè)重要功能區(qū)域C 端活化區(qū)域1(carboxyl-terminal activating region 1，CTAR1；第187～231位氨基酸殘基)和CTAR2(第352～386位氨基酸殘基)使miR-29b表達(dá)上調(diào)，進(jìn)而抑制原癌基因TCL1(T-cell leukemia gene 1)[58]。有意思的是，EBV編碼的BART組miRNA可與LMP1基因組3′-UTR結(jié)合，調(diào)節(jié)LMP1表達(dá)，表明在EBV與腫瘤發(fā)病的關(guān)系中，既有病毒編碼miRNA的參與，也有宿主編碼miRNA的調(diào)節(jié)[59]。

除EBV外，其他病毒感染也可導(dǎo)致宿主miRNA表達(dá)量發(fā)生變化，引起腫瘤形成。例如，人乳頭瘤病毒(human papillomavirus，HPV)編碼病毒E6蛋白抑制p53基因早有報(bào)道。近年來又發(fā)現(xiàn)p53能直接與miR-34a第一外顯子內(nèi)的靶序列相結(jié)合，促進(jìn)miR-34a的轉(zhuǎn)錄。p53基因表達(dá)或功能異常會(huì)導(dǎo)致其對(duì)miR-34a的刺激信號(hào)減少，降低miR-34a表達(dá)，最終造成細(xì)胞無限增殖和腫瘤形成[60]。人T細(xì)胞白血病病毒1型(human T-cell leukemia virus 1，HTLV-1)感染人體后引起miR-93和miR-130b表達(dá)上調(diào)，其3′-UTR可與抑癌蛋白TP53INP1(tumor protein 53-induced nuclear protein 1)結(jié)合，使其表達(dá)下調(diào)，最終引起成人T細(xì)胞白血病(adult T-cell leukemia，ATL)[61]。

3.2 宿主miRNA與病毒感染

宿主編碼miRNA除與腫瘤相關(guān)外，還參與病毒感染的致病過程。miR-199a-3p和miR-210可分別作用于乙型肝炎病毒(hepatitis B virus，HBV)的S和前S基因，抑制病毒復(fù)制，減少HBV表面抗原(HBV surface antigen，HBsAg)的表達(dá)而不影響細(xì)胞增殖。miR-1雖然不能直接作用于HBV，但可調(diào)節(jié)宿主基因，間接促進(jìn)HBV復(fù)制、轉(zhuǎn)錄、抗原表達(dá)和產(chǎn)物分泌[62-63]。miR-24和miR-93可與水皰性口炎病毒(vesicular stomatitis virus， VSV)基因組中編碼L蛋白和P蛋白的區(qū)域相結(jié)合，從而干擾病毒復(fù)制[64]。miR-370可通過與其受體核因子IA(nuclear factor IA，NFIA)結(jié)合，抑制HBV基因的表達(dá)和復(fù)制[65]。miR-28、miR-125b、miR-150、miR-223 和miR-382等多種宿主miRNA可被HIV-1調(diào)控而高表達(dá)，進(jìn)而降低HIV-1轉(zhuǎn)錄水平，導(dǎo)致病毒在CD4+T細(xì)胞中潛伏感染[66]。miRNA還可靶向結(jié)合HIV-1基因組，這些基因組高度保守，其中miR-29a和miR-29b結(jié)合nef基因，miR-149結(jié)合vpr基因，miR-378結(jié)合env基因，miR-324-5p結(jié)合vif基因。這5種miRNA均在HIV-1感染的T細(xì)胞中表達(dá)，提示其與HIV-1感染密切相關(guān)[67]。宿主感染甲型流感病毒后，miR-29表達(dá)上調(diào)約50倍，抑制DNA甲基轉(zhuǎn)移酶(DNA methyltransferase，DNMT)活性，進(jìn)一步誘導(dǎo)環(huán)氧化酶2(cyclooxygenase 2，COX2)，啟動(dòng)信號(hào)轉(zhuǎn)導(dǎo)途徑，最終達(dá)到抗病毒的作用[68]。在脊髓灰質(zhì)炎病毒疫苗研制過程中，miR-555因可降低病毒復(fù)制所需的核不均一核糖核蛋白(heterogeneous nuclear ribonucleoprotein，hnRNP) C1/C2復(fù)制水平而表現(xiàn)出抗病毒活性[69]。

3.3 宿主miRNA的應(yīng)用

宿主編碼的miRNA在臨床上有較好的應(yīng)用前景。① miRNA的變化可體現(xiàn)臨床預(yù)后。高致病性流感病毒感染時(shí)機(jī)體中某些miRNA分子表達(dá)異常，而在其他非致命性病原感染時(shí)表達(dá)無明顯變化。如miR-21和miR-223分別在H5N1禽流感病毒和高致病性甲型H1N1流感病毒感染時(shí)明顯上調(diào)。這些miRNA分子與宿主體內(nèi)的細(xì)胞因子相互作用，影響炎癥反應(yīng)和細(xì)胞凋亡，預(yù)后不良[70-71]。②miRNA可作為疾病分子診斷指標(biāo)。miRNA相比于蛋白質(zhì)等其他診斷指標(biāo)有許多優(yōu)點(diǎn)，如血液、尿液中miRNA穩(wěn)定性強(qiáng)；樣本采集方便，用量少；miRNA出現(xiàn)變化的時(shí)間早，有助于疾病的早期診斷。miRNA在組織中有相對(duì)特異的表達(dá)，為其在診斷中的應(yīng)用提供了理論依據(jù)[24]。③miRNA可作為抗病毒治療藥物。miRNA藥物的研發(fā)目前仍處于起步階段，僅丹麥Santaris Pharma公司宣布其研制的鎖核酸(locked nucleic acid，LNA)SPC3649有作為抗病毒藥物的應(yīng)用前景。SOC3649是miR-122拮抗劑，可與miR-122的5′-UTR結(jié)合，抑制miR-122-HCV復(fù)合物形成，從而抑制病毒復(fù)制。目前該藥物正在美國(guó)、荷蘭、德國(guó)、波蘭、羅馬尼亞和斯洛伐克進(jìn)行Ⅱ期臨床試驗(yàn)，并展現(xiàn)出很好的抗病毒效果[72-75]。

4 結(jié)語(yǔ)

miRNA分子是由RNA聚合酶Ⅱ/Ⅲ轉(zhuǎn)錄而來的長(zhǎng)度約22 nt的內(nèi)源性非編碼小RNA分子，其可與靶mRNA結(jié)合，參與基因的轉(zhuǎn)錄后調(diào)節(jié)。miRNA調(diào)控通路的發(fā)現(xiàn)使人們以全新的視角重新審視病毒與宿主的相互關(guān)系。病毒編碼的miRNA可降低其對(duì)宿主CTL、NK細(xì)胞的敏感性，逃避免疫反應(yīng)；有的甚至可對(duì)病毒自身復(fù)制起正調(diào)控作用。宿主編碼的大多數(shù)miRNA可起保護(hù)作用，其表達(dá)失調(diào)可導(dǎo)致腫瘤形成和抗病毒能力減弱。少數(shù)miRNA可與靶基因5′-UTR結(jié)合，促進(jìn)病毒復(fù)制。目前，人們已嘗試?yán)胢iRNA進(jìn)行疾病診斷和藥物治療。相信隨著研究的深入，會(huì)有更多的基于miRNA的抗病毒預(yù)防和治療策略被發(fā)現(xiàn)。

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. AN Jing, E-mail: anjing@ccmu.edu.cn

Functions of microRNAs in virus-host interactions

WEI Jianchun, AN Jing

InstituteofPathogenicBiology,CapitalMedicalUniversity,Beijing100069,China

microRNAs (miRNAs) are a class of non-coding small RNAs with the length of about 22 nucleotides. More than 35 000 miRNAs have been found in plants, animals and viruses since its discovery inCaenorhabditiselegansin 1993. They participate in a variety of biological processes involved in cell differentiation, apoptosis, metabolism, signal transduction, immune responses, and act as critical transcription factors. miRNAs can be encoded both by viruses and host cells. Virus-encoded miRNAs can alter the internal environment of host, and host-encoded miRNAs also have effect on survival of virus. This article aims to review the functions of miRNAs in virus-host interactions.

microRNA; Herpes virus; Tumor; Virus-host interaction

國(guó)家自然科學(xué)基金(81271839、81471957)

安靜

2015-12-03)