魏勇，何玉蘭，鄭學(xué)禮

綜 述

RNAi在抗蚊媒病毒感染中的研究進(jìn)展

魏勇，何玉蘭，鄭學(xué)禮

南方醫(yī)科大學(xué)公共衛(wèi)生學(xué)院病原生物學(xué)系，廣州 510515

蚊媒病因具有較高的發(fā)病率和傳播率使其成為全球關(guān)注的重要公共衛(wèi)生問(wèn)題。蚊蟲(chóng)作為蚊媒病的傳播媒介，研究其與蚊媒病毒兩者之間的相互作用機(jī)制將有助于蚊媒病的防控。蚊蟲(chóng)抵御蚊媒病毒的先天免疫降低和病毒成功逃避蚊蟲(chóng)免疫屏障為病毒在蚊蟲(chóng)體內(nèi)的持續(xù)感染和蚊媒病的暴發(fā)流行造成了潛在風(fēng)險(xiǎn)。RNA干擾(RNA interference, RNAi)途徑作為蚊蟲(chóng)體內(nèi)強(qiáng)大的抗病毒防御屏障，通過(guò)產(chǎn)生多種小RNA降解病毒RNA，從而達(dá)到抑制病毒復(fù)制和傳播的目的。本文對(duì)小干擾RNA (small interfering RNA, siRNA)、微小RNA (microRNA, miRNA)、Piwi蛋白相作用RNA (Piwi-interacting RNA, piRNA)等3種小分子RNA在蚊蟲(chóng)體內(nèi)發(fā)揮抗蚊媒病毒感染的先天免疫機(jī)制的相關(guān)研究進(jìn)行了綜述，以期為蚊媒病的防控提供理論參考。

蚊蟲(chóng)；蚊媒病毒；siRNA；miRNA；piRNA

蚊媒病是一類由病媒蚊蟲(chóng)傳播的自然疫源性疾病，常見(jiàn)的有流行性乙型腦炎、登革熱、黃熱病等。隨著全球氣候變暖、交通運(yùn)輸便捷和旅游業(yè)發(fā)展，蚊蟲(chóng)在全球范圍內(nèi)快速擴(kuò)張，這為蚊媒病的暴發(fā)流行和傳播擴(kuò)散構(gòu)成了潛在風(fēng)險(xiǎn)。絕大多數(shù)蚊媒病毒以及在全球發(fā)病率和死亡率占較大比重的均是RNA病毒，如黃病毒科黃病毒屬(正鏈RNA病毒)、披膜病毒科甲病毒屬(正鏈RNA病毒)、布尼亞病毒科白蛉病毒屬(負(fù)鏈RNA病毒)[1,2]。黃病毒科黃病毒屬包括黃熱病病毒(yellow fever virus, YFV)、登革病毒(Dengue virus, DENV)、乙型腦炎病毒(Japanese encephalitis virus, JEV)、西尼羅河病毒(West Nile virus, WNV)和寨卡病毒(Zika virus, ZIKV)等[3]，披膜病毒科甲病毒屬包括基孔肯雅病毒(Chikungunya virus, CHIKV)、辛德畢斯病毒(Sindbis virus, SINV)、塞姆利基森林病毒(Semliki forest virus, SFV)、羅斯河病毒(Ross river virus, RRV)等[4]，布尼亞病毒科白蛉病毒屬包括托斯卡納病毒(Toscana virus, TOSV)、裂谷熱病毒(Rift Valley fever virus, RVFV)等[5]。在過(guò)去的幾十年間，登革熱至少在128個(gè)國(guó)家或地區(qū)暴發(fā)流行，每年平均有3.9億人口感染登革熱，登革熱一直是重點(diǎn)關(guān)注的全球公共衛(wèi)生問(wèn)題[6]。寨卡病毒病是近年來(lái)新興的蚊媒傳播性疾病，2016年2月世界衛(wèi)生組織(WHO)宣布將寨卡疫情列為全球緊急公共衛(wèi)生事件。自從2015年巴西發(fā)生大規(guī)模寨卡病毒感染疫情后，目前已有64個(gè)國(guó)家和地區(qū)報(bào)告了寨卡疫情[7]。寨卡病毒感染引起的成人格林-巴利綜合征(Guillain-Barre syndrome, GBS)和新生兒出生缺陷，如產(chǎn)前感染所致的小頭畸形，在近年來(lái)引發(fā)了全球廣泛關(guān)注[8]。因目前缺乏蚊媒病相應(yīng)的有效疫苗，抑制病毒在蚊蟲(chóng)體內(nèi)復(fù)制和阻斷病毒傳播將是控制蚊媒病暴發(fā)流行的有效途徑[9]。因此，研究蚊蟲(chóng)體內(nèi)抗蚊媒病毒感染的先天免疫機(jī)制將有助于制定相應(yīng)的蚊媒病控制策略。本文將對(duì)目前蚊蟲(chóng)體內(nèi)3大主要抗病毒的RNAi途徑的相關(guān)研究進(jìn)行綜述，以期為蚊媒病的防控提供理論參考。

1 蚊蟲(chóng)體內(nèi)三大主要的RNAi途徑

蚊蟲(chóng)的先天免疫屏障和蚊媒病毒的免疫逃避機(jī)制是影響病毒在蚊蟲(chóng)體內(nèi)成功復(fù)制和傳播的關(guān)鍵因素。蚊蟲(chóng)體內(nèi)抗病毒的效應(yīng)分子(抗菌肽(antimicro-bial peptide, AMP)、活性氧(reactive oxygen species, ROS)和酚氧化酶級(jí)聯(lián)反應(yīng)的組分等)，以及效應(yīng)分子所依賴的信號(hào)通路(JAK-STAT、Toll和Imd等信號(hào)通路)是蚊蟲(chóng)體內(nèi)免疫防御的重要方面[10~12]。此外，RNA干擾(RNAi)途徑是蚊蟲(chóng)體內(nèi)最為強(qiáng)大的抗病毒防御體系[13]。RNAi是指由雙鏈RNA(dsRNA)誘發(fā)的具有高度保守的小RNA片段可高效特異性降解同源mRNA的現(xiàn)象，是轉(zhuǎn)錄后水平的基因沉默(post- transcriptional gene silencing, PTGS)。RNAi途徑主要包含3種類型的小RNA：小干擾RNA (siRNA)、微小RNA (miRNA)和Piwi蛋白相作用RNA (piRNA)，其中siRNA為蚊蟲(chóng)體內(nèi)抗病毒免疫的主要小RNA分子[13~15]。RNAi具有高度的序列特異性，嚴(yán)格按照堿基互補(bǔ)配對(duì)原則與同源基因的mRNA結(jié)合并進(jìn)行降解，從而實(shí)現(xiàn)針對(duì)目的基因的精準(zhǔn)沉默；RNAi具有高效抑制基因表達(dá)的特性，表型可達(dá)到缺失突變體表型的程度；RNAi還具有可遺傳性和可傳播性，RNA干擾效應(yīng)能穩(wěn)定遺傳給下一代，也可穿過(guò)細(xì)胞界限，傳播至擴(kuò)散處細(xì)胞乃至整個(gè)機(jī)體[16,17]。利用RNAi特性發(fā)展的RNAi技術(shù)可廣泛地應(yīng)用于基因功能的探索、傳染性疾病和惡性腫瘤的治療領(lǐng)域[18~21]。

2 siRNA在蚊蟲(chóng)體內(nèi)的抗病毒作用

siRNA途徑可分為內(nèi)源性通路和外源性通路。內(nèi)源性siRNA一般由細(xì)胞內(nèi)基因雙向轉(zhuǎn)錄形成的部分互補(bǔ)配對(duì)或由RNA依賴性RNA聚合酶(RNA- dependent RNA polymerase, RDRP)進(jìn)行的RNA鏈復(fù)制等形成的dsRNA經(jīng)剪切修飾而產(chǎn)生，在生物體不同生長(zhǎng)發(fā)育時(shí)期發(fā)揮調(diào)控作用。外源性siRNA一般是由轉(zhuǎn)基因技術(shù)或病毒感染細(xì)胞后產(chǎn)生的復(fù)制中間體—dsRNA經(jīng)過(guò)核糖核酸酶III(RNase III)家族中的Dicer-2核酸內(nèi)切酶剪切成長(zhǎng)度約為21~25 nt的雙鏈小RNA分子[22,23]。細(xì)胞內(nèi)siRNA通過(guò)與AGO、TRBP和PACT等蛋白分子結(jié)合形成RNA誘導(dǎo)的沉默復(fù)合物(RNA-induced silencing complex, RISC)，siRNA的隨從鏈被降解，引導(dǎo)鏈通過(guò)堿基互補(bǔ)配對(duì)的方式找到靶基因的mRNA或同源的病毒RNA，然后RISC中的Ago-2蛋白降解其mRNA或病毒RNA，阻止翻譯表達(dá)或病毒復(fù)制(圖1)[24,25]。

Li等[26]首次在岡比亞按蚊()細(xì)胞系中驗(yàn)證了siRNA的抗病毒作用，并表明其抑制效應(yīng)依賴于Ago-2蛋白。Sánchez-Vargas等[27]研究發(fā)現(xiàn)沉默埃及伊蚊() siRNA通路會(huì)增加蚊蟲(chóng)體內(nèi)登革2型病毒的復(fù)制，這表明siRNA通路在蚊蟲(chóng)體內(nèi)病毒復(fù)制過(guò)程中發(fā)揮抑制作用。Khoo等[28]通過(guò)轉(zhuǎn)基因技術(shù)破壞埃及伊蚊中腸的siRNA通路，發(fā)現(xiàn)這樣會(huì)增加中腸內(nèi)辛德畢斯病毒(SINV)的復(fù)制和播散率。Basu等[29]通過(guò)基因敲除抑制埃及伊蚊Dcr-2酶的表達(dá)，發(fā)現(xiàn)蚊蟲(chóng)體內(nèi)抗辛德畢斯病毒的免疫反應(yīng)下降；另外，Dcr-2基因突變型的埃及伊蚊較野生型的蚊蟲(chóng)體內(nèi)具有顯著增加的黃熱病病毒復(fù)制水平[30]。多項(xiàng)研究表明，在敲除siRNA通路的相關(guān)成分后，成蚊體內(nèi)或培養(yǎng)的蚊蟲(chóng)細(xì)胞系中的病毒復(fù)制水平會(huì)顯著升高[27,31]。成蚊或不同細(xì)胞系感染蚊媒病毒后會(huì)導(dǎo)致該病毒來(lái)源的siRNA (virus-derived small interfering RNA, vsiRNA)產(chǎn)生[32,33]。Myles等[34]研究表明vsiRNA對(duì)蚊蟲(chóng)體內(nèi)抗甲病毒感染具有重要調(diào)控作用。能夠表達(dá)dsRNA結(jié)合蛋白和病毒RNA沉默抑制因子(viral suppressors of RNA silencing, VSRs)的重組甲病毒感染埃及伊蚊和岡比亞按蚊后，蚊蟲(chóng)體內(nèi)的vsiRNA顯著下降，從而導(dǎo)致病毒復(fù)制量和蚊蟲(chóng)死亡率顯著增加。

圖1 siRNA的生物合成和作用機(jī)制

單鏈RNA逆轉(zhuǎn)錄形成雙鏈RNA，經(jīng)Dicer-2核酸內(nèi)切酶剪切成雙鏈小RNA分子，其引導(dǎo)鏈與Ago-2等相應(yīng)蛋白組成RNA誘導(dǎo)沉默復(fù)合物，通過(guò)堿基互補(bǔ)配對(duì)的方式結(jié)合靶標(biāo)RNA，并將該靶標(biāo)RNA降解。

蚊媒病毒在受到蚊蟲(chóng)宿主先天免疫消除的同時(shí)，也在不斷進(jìn)化適應(yīng)宿主的生理環(huán)境，并對(duì)抗媒介蚊蟲(chóng)的抗病毒免疫途徑。通過(guò)鑒別蚊媒病毒基因組中編碼的病毒RNA沉默抑制因子(VSRs)，了解病毒蛋白對(duì)蚊蟲(chóng)免疫途徑的拮抗作用，將有助于理解蚊媒病毒在蚊蟲(chóng)體內(nèi)長(zhǎng)期感染和傳播的機(jī)制，并應(yīng)用于蚊媒病的防控[35]。布尼亞維拉病毒(Bunyamwera virus, BUNV)S片段上的非結(jié)構(gòu)蛋白(non-structure proteins, NSs)是VSRs，NSs缺陷性BUNV在Dcr-2缺陷性的蚊蟲(chóng)細(xì)胞系中的復(fù)制水平要高于在正常蚊蟲(chóng)細(xì)胞系中的復(fù)制水平，NSs缺陷性BUNV在埃及伊蚊體內(nèi)的感染能力要低于野生型BUNV[36]。Kaku-mani等[37]通過(guò)體外實(shí)驗(yàn)證明登革熱病毒(DENV) NS4B蛋白能夠干擾Dicer對(duì)siRNA的加工處理過(guò)程。哺乳動(dòng)物細(xì)胞中的基因沉默實(shí)驗(yàn)顯示NS4B蛋白的跨膜結(jié)構(gòu)域3 (transmembrane domain 3, TMD3)和TME5參與VSRs抑制病毒增殖的活性，其具體機(jī)制目前尚不明確。Samuel等[38]研究發(fā)現(xiàn)在Dcr-2缺陷性的蚊蟲(chóng)細(xì)胞系中表達(dá)黃病毒衣殼蛋白(yellow fever virus capsid, YFC)的SINV與不表達(dá)YFC的SINV的增殖能力和毒力相似，并且驗(yàn)證了YFC作為VSRs拮抗siRNA途徑。YFC對(duì)siRNA途徑拮抗作用可能是非特異性結(jié)合雙鏈RNA(dsRNA)，干擾Dicer產(chǎn)生vsiRNA。雖然VSRs有多種不同的蛋白，但它與dsRNA非特異性結(jié)合是探討其拮抗作用的主要內(nèi)容。

3 miRNA在蚊蟲(chóng)體內(nèi)的抗病毒作用

miRNA是一類內(nèi)源性的非編碼小RNA (18~ 25 nt)，通過(guò)降解mRNA或抑制mRNA翻譯來(lái)調(diào)控靶基因轉(zhuǎn)錄后表達(dá)水平[39]。與siRNA途徑相似，miRNA途徑也始于dsRNA剪切成小的雙鏈RNA，其中一條引導(dǎo)鏈加載到RISC中，然后RISC中Ago-2蛋白降解靶基因的mRNA或同源的病毒RNA[40]。miRNA與siRNA途徑的主要區(qū)別在于所發(fā)生的亞細(xì)胞結(jié)構(gòu)位置和所參與的效應(yīng)蛋白分子[41]。siRNA的轉(zhuǎn)錄、剪切和加工過(guò)程主要發(fā)生在細(xì)胞質(zhì)中，而編碼miRNA的基因在宿主RNA聚合酶Ⅱ的作用下轉(zhuǎn)錄成miRNA初始轉(zhuǎn)錄物(primary miRNA, pri-miRNA)，然后由Drosha剪切加工成miRNA前體物(precursor miRNA, pre-miRNA)，這一過(guò)程均是在細(xì)胞核內(nèi)完成。pre-miRNA輸出到細(xì)胞質(zhì)后，由Dicer-1進(jìn)一步加工至成熟的miRNA，并加載到RISC中發(fā)揮RNA干擾作用(圖2)[42]。

多種蚊媒病毒均利用宿主miRNA通路來(lái)逃避宿主的抗病毒免疫反應(yīng)，從而增加病毒復(fù)制和致病力[43]。Hussain等[44]在西尼羅河病毒(WNV)RNA序列的3￠端非編碼區(qū)發(fā)現(xiàn)了類似miRNA的小RNA片段，并通過(guò)Northern印記雜交的方法檢測(cè)到感染W(wǎng)NV的埃及伊蚊和白紋伊蚊()細(xì)胞系中存在一種病毒來(lái)源的成熟miRNA，命名為KUN-miR-1。KUN-miR-1通過(guò)上調(diào)轉(zhuǎn)錄因子GATA4的表達(dá)來(lái)促進(jìn)病毒在蚊蟲(chóng)細(xì)胞內(nèi)的增殖。Hussain 等[45]通過(guò)二代測(cè)序技術(shù)發(fā)現(xiàn)感染登革2型病毒(DENV-2)的埃及伊蚊體內(nèi)含有6種病毒來(lái)源的miRNA樣的小RNA，稱為vsRNA 1~6；其中vsRNA5已證實(shí)與病毒增殖有關(guān)。蚊蟲(chóng)體內(nèi)miRNA通路關(guān)鍵分子的功能喪失性突變將有助于鑒定其分子特性，并確定KUN-miR-1和DENV-2-vsRNA 1~6的生物發(fā)生機(jī)制和抗病毒免疫機(jī)制。

圖2 miRNA的生物合成和作用機(jī)制

含miRNA序列的DNA經(jīng)過(guò)轉(zhuǎn)錄后形成初始miRNA，然后經(jīng)Drosha和Dicer-1等蛋白剪切加工修飾后形成成熟的miRNA，成熟的miRNA與Ago-1等相應(yīng)蛋白組成RNA誘導(dǎo)沉默復(fù)合物，通過(guò)堿基互補(bǔ)配對(duì)的方式結(jié)合靶標(biāo)RNA，并將該靶標(biāo)RNA降解或抑制mRNA翻譯。

當(dāng)蚊蟲(chóng)感染蚊媒病毒后體內(nèi)會(huì)出現(xiàn)多種miRNA差異性表達(dá)[46,47]。Su等[48]利用含DENV-2的血餐以及不含DENV-2的血餐分別喂食白紋伊蚊，鑒定蚊蟲(chóng)中腸內(nèi)差異性表達(dá)的miRNA，相比于喂食不含DENV-2血餐的白紋伊蚊，一共有43個(gè)miRNA上調(diào)，4個(gè)miRNA下調(diào)；并且上調(diào)的miRNA中aal-miR- 4728-5p瞬時(shí)轉(zhuǎn)入C6/36蚊蟲(chóng)細(xì)胞后能夠增強(qiáng)DENV-2在細(xì)胞內(nèi)的復(fù)制。Su等[49]再次利用含DENV-2的血餐喂食白紋伊蚊，將感染上DENV-2與未感染上DENV-2的白紋伊蚊中腸內(nèi)miRNA進(jìn)行差異性分析，發(fā)現(xiàn)感染上DENV-2的白紋伊蚊中腸內(nèi)有15個(gè)miRNA上調(diào)，2個(gè)miRNA下調(diào)。其中miR-1767和miR-276-3p能夠增強(qiáng)DENV-2在C6/36細(xì)胞內(nèi)的復(fù)制，而miR-4448抑制DENV-2在C6/36細(xì)胞內(nèi)的復(fù)制。

4 piRNA在蚊蟲(chóng)體內(nèi)的抗病毒作用

piRNA途徑可在siRNA途徑缺陷的條件下進(jìn)行抗病毒免疫，是RNAi介導(dǎo)的抗病毒免疫應(yīng)答的相互補(bǔ)充[50]。與siRNA/miRNA相比，piRNA的生成不依賴Dicer，而依賴PIWI亞家族蛋白；piRNA的長(zhǎng)度約為26~32 nt，piRNA基因簇主要分別在轉(zhuǎn)座子和重復(fù)序列等區(qū)域；piRNA的3'端會(huì)出現(xiàn)甲基化修飾，可能與其穩(wěn)定性或功能有關(guān)[51~53]。piRNA的生成涉及3種PIWI蛋白，包括Piwi、Aub和Ago-3，共同形成piRNA誘導(dǎo)的沉默復(fù)合物(piRNA-induced silencing complex, piRISC)[54]。對(duì)于piRNA的生成，目前提出了“乒乓”循環(huán)擴(kuò)增模型，piRNA從轉(zhuǎn)錄前體物中循環(huán)擴(kuò)增[55]。反義鏈piRNA與Aub和Piwi結(jié)合形成具有核酸酶活性的piRNA復(fù)合物(piRNA co-mplex, piRC)，piRC能結(jié)合正義鏈前體piRNA并將其剪切加工成具有成熟5￠端的前體piRNA，然后該正義鏈前體piRNA經(jīng)Zuc等酶剪切3￠末端形成成熟的正義鏈piRNA；反之，正義鏈piRNA與Ago-3結(jié)合形成piRC，然后以同樣的方式形成反義鏈piRNA (圖3)[56]。piRNA途徑在生殖遺傳、配子形成、胚胎發(fā)育、基因轉(zhuǎn)座、基因沉默和病毒增殖等方面均有調(diào)控作用。

圖3 piRNA的生物合成和作用機(jī)制

單鏈RNA經(jīng)剪切形成前體piRNA，然后經(jīng)Zuc等酶剪切加工后形成成熟的piRNA，成熟的piRNA與Piwi、Aub和Ago-3等蛋白組成piRNA誘導(dǎo)沉默復(fù)合物，通過(guò)堿基互補(bǔ)配對(duì)的方式結(jié)合靶標(biāo)RNA，并將該靶標(biāo)RNA降解。虛線框內(nèi)為piRNA的“乒乓”循環(huán)擴(kuò)增模型。

蚊蟲(chóng)或蚊蟲(chóng)細(xì)胞系感染蚊媒病毒后，能夠產(chǎn)生一類依賴“乒乓”模型的病毒來(lái)源的piRNA (virus- derived piRNA, vpiRNA)，這些vpiRNA不同于以往研究中來(lái)源于重復(fù)序列元件或piRNA簇的piRNA[57,58]。Morazzani等[57]在感染有基孔肯亞熱病毒(CHIKV)的埃及伊蚊和白紋伊蚊體內(nèi)檢測(cè)到vpiRNA。Miesen等[59]用SINV感染埃及伊蚊細(xì)胞系后，通過(guò)免疫沉淀反應(yīng)和小RNA的Northern免疫印跡檢測(cè)到了Ago-3和Piwi-5蛋白特異性富集的vpiRNA。通過(guò)對(duì)這類vpiRNA測(cè)序分析，顯示反義鏈vpiRNA傾向于與Piwi-5結(jié)合，而正義鏈vpiRNA傾向于與Ago-3結(jié)合，這也表明了這兩種蛋白在“乒乓”模型中的作用機(jī)制。抑制vpiRNA在siRNA途徑缺陷的蚊蟲(chóng)細(xì)胞系中表達(dá)，將會(huì)加重受病毒感染細(xì)胞的病變程度，這體現(xiàn)了piRNA途徑在siRNA途徑缺陷的蚊蟲(chóng)細(xì)胞系中的抗病毒作用[57]。Schnettler等[60]通過(guò)深度測(cè)序檢測(cè)到塞姆利基森林病毒(SFV)來(lái)源的piRNA，敲除Piwi-4基因后會(huì)導(dǎo)致Aag2埃及伊蚊細(xì)胞內(nèi)SFV復(fù)制增加，表明了piRNA途徑在抗病毒免疫中的重要作用。

5 結(jié)語(yǔ)與展望

每年全球均有大量的蚊媒病暴發(fā)流行，并且目前大部分的蚊媒病缺乏有效的疫苗進(jìn)行預(yù)防，所以阻止蚊媒病毒傳播一直是蚊媒病預(yù)防控制的重要任務(wù)。目前有關(guān)化學(xué)殺蟲(chóng)劑和生物防治等方面的防控措施主要是通過(guò)控制蚊蟲(chóng)數(shù)量來(lái)控制蚊媒病的暴發(fā)流行。病毒感染和蚊蟲(chóng)防御機(jī)制以及兩者動(dòng)態(tài)平衡的演變過(guò)程一直是科研工作者關(guān)注和探索的問(wèn)題，深入了解蚊蟲(chóng)先天免疫系統(tǒng)如何抵御病毒感染，病毒如何在蚊蟲(chóng)體內(nèi)持續(xù)穩(wěn)定增殖，以及不同蚊蟲(chóng)種類或病毒株如何影響疾病暴發(fā)流行等方面內(nèi)容，將有助于提高現(xiàn)有策略的有效性，并提出新的蚊媒控制策略。RNAi途徑作為蚊蟲(chóng)體內(nèi)主要的抗病毒防御體系，目前我國(guó)科研工作者對(duì)蚊蟲(chóng)RNAi途徑的研究主要集中在相關(guān)小RNA分子的作用機(jī)制，然而通過(guò)基因編輯加強(qiáng)蚊蟲(chóng)RNAi抗病毒免疫的相關(guān)研究較少，將轉(zhuǎn)基因蚊廣泛有效地應(yīng)用于蚊媒病防控也是任重道遠(yuǎn)。

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Research progress in RNA interference against the infection of mosquito-borne viruses

Yong Wei, Yulan He, Xueli Zheng

Mosquito-borne diseases have become an important public health issue of global concern because of their high incidence and transmission rate. As a vector for mosquito-borne diseases, studying the interaction mechanism between mosquitoes and mosquito-borne viruses will help control mosquito-borne diseases. The impaired innate immunity and immune barriers evasion caused by mosquito-borne viruses in mosquitoes pose a potential risk for the persistent infection of the virus in mosquitoes and the outbreak of mosquito-borne diseases. The RNA interference (RNAi) pathway, as a powerful antiviral defense barrier in mosquitoes, can inhibit viral replication and transmission by producing a variety of small RNAs to degrade viral RNA. In this review, we summarize the related studies on the innate immune mechanism against mosquito- borne virus infection in mosquitoes about small interfering RNA (siRNA), microRNA (miRNA), and Piwi-interacting RNA (piRNA), aiming to provide a theoretical reference for the prevention and control of mosquito-borne diseases.

Mosquito; Mosquito-borne viruses; siRNA; miRNA; piRNA

2019-10-15;

2019-12-14

國(guó)家自然科學(xué)基金項(xiàng)目(編號(hào)：31630011)，廣東省自然科學(xué)基金項(xiàng)目(編號(hào)：2017A030313625)和廣州市科技計(jì)劃項(xiàng)目(編號(hào)：201804020084)資助[Supported by National Natural Science Foundation of China (No. 31630011), Natural Science Foundation of Guangdong Province of China (No. 2017A030313625), Science and Technology Planning Project of Guangzhou City (No. 201804020084)]

魏勇，在讀博士研究生，研究方向：傳染病預(yù)防與控制。E-mail: smuweiyong@163.com

鄭學(xué)禮，博士，教授，研究方向：傳染病預(yù)防與控制。E-mail: zhengxueli2001@126.com

10.16288/j.yczz.19-262

2020/1/2 18:34:26

URI: http://kns.cnki.net/kcms/detail/11.1913.R.20191231.1147.003.html

(責(zé)任編委: 岑山)