Research progress in mosquito-borne flaviviruses transmission and the development of vaccines and drugs

doi:10.12211/2096-8280.2022-069

Abstract

Abstract:

Mosquito-borne viruses transmit between hosts and mosquito carriers through mosquito biting, which cause hundreds of millions of infections each year. These viral infections result in serious human diseases such as hemorrhagic fever, biphasic fever, arthritis, encephalitis and meningitis, which can lead to death if proper treatment is not available. Most mosquito-borne viruses are RNA viruses, with the flavivirus family as the most prevalent ones, including dengue virus, Zika virus, yellow fever virus, Japanese encephalitis virus and West Nile virus. Although there are effective vaccines for a few mosquito-borne flaviviruses, such as those for yellow fever virus and Japanese encephalitis virus, there are still no effective preventive vaccines and antiviral therapies for most mosquito-borne flaviviruses. Therefore, a comprehensive understanding of the mechanisms underlying the infection and transmission of mosquito-borne flaviviruses between vertebrate hosts and mosquitoes would provide insights for vaccine and drug development, enabling us to more effectively predict and control the transmission of mosquito-borne flavivirus and occurrence of the epidemics in the future, and providing solutions for addressing the public health threats posed by arboviruses. In this article, we firstly describe the biological and epidemiological characteristics of mosquito-borne flaviviruses, introduce the transmission routes and carrier models of mosquito-borne flaviviruses, and summarize the current research on the transmission and infection mechanisms of mosquito-borne flaviviruses between hosts and carriers. Furthermore, we highlight the development of novel vaccines and strategies for screening drugs to fight against mosquito-borne flaviviruses, providing an outlook for future research and development of vaccines and antiviral drugs.

Key words: mosquito-borne flavivirus, mosquito vector, infection and transmission, pathogenesis, vaccine and drug

摘要：

关键词: 蚊媒黄病毒, 蚊虫媒介, 感染与传播, 致病机制, 疫苗与药物

CLC Number:

Q939.93

YU Xi, LIU Jianying, CHENG Gong. Research progress in mosquito-borne flaviviruses transmission and the development of vaccines and drugs[J]. Synthetic Biology Journal, 2023, 4(2): 347-372.

余茜, 刘建英, 程功. 蚊媒黄病毒传播机制及疫苗与药物研发进展[J]. 合成生物学, 2023, 4(2): 347-372.

Figures/Tables 4

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疫苗名称	疫苗种类	抗原	针对病毒种类	疫苗开发阶段	开发者
17D	减毒活疫苗	E蛋白	YFV	已获得许可	[185]
SA14-14-2	减毒活疫苗	E蛋白	JEV	已获得许可	CDIBP
TV003	减毒活疫苗	prM-E	DENV 1～4	临床三期	NIAID
DENVax	减毒活疫苗	prM-E	DENV 1～4	临床三期	Takeda
TDENV-PIV	灭活疫苗	C-prM-E-NS1/3/5	DENV 1～4	临床一期	GSK, Fiocruz & WRAIR
ZPIV	灭活疫苗	E蛋白	ZIKV	临床一期	WRAIR/NIAID
CYD-TDV(Dengvaxia)	重组疫苗	prM-E	DENV 1～4	已获得许可	Sanofi Pasteur
ChimeriVax-WN02	重组疫苗	prM-E	WNV	临床二期	Sanofi Pasteur
V180	重组疫苗	E蛋白	DENV 1～4	临床一期	Merck
ZIKV-VLP	VLPs	C-prM-E-NS2B/NS3	ZIKV	动物实验	[186]
DENV-VLP	VLPs	prM-E	DENV 1～4	临床前	[187]
GLS-5700	DNA疫苗	prM-E/NS1	ZIKV	临床一期	Inovio GeneOne
IgEsig-prM-E-LNP	mRNA疫苗	prM-E	ZIKV	动物实验	[188]

疫苗名称	疫苗种类	抗原	针对病毒种类	疫苗开发阶段	开发者
17D	减毒活疫苗	E蛋白	YFV	已获得许可	[185]
SA14-14-2	减毒活疫苗	E蛋白	JEV	已获得许可	CDIBP
TV003	减毒活疫苗	prM-E	DENV 1～4	临床三期	NIAID
DENVax	减毒活疫苗	prM-E	DENV 1～4	临床三期	Takeda
TDENV-PIV	灭活疫苗	C-prM-E-NS1/3/5	DENV 1～4	临床一期	GSK, Fiocruz & WRAIR
ZPIV	灭活疫苗	E蛋白	ZIKV	临床一期	WRAIR/NIAID
CYD-TDV(Dengvaxia)	重组疫苗	prM-E	DENV 1～4	已获得许可	Sanofi Pasteur
ChimeriVax-WN02	重组疫苗	prM-E	WNV	临床二期	Sanofi Pasteur
V180	重组疫苗	E蛋白	DENV 1～4	临床一期	Merck
ZIKV-VLP	VLPs	C-prM-E-NS2B/NS3	ZIKV	动物实验	[186]
DENV-VLP	VLPs	prM-E	DENV 1～4	临床前	[187]
GLS-5700	DNA疫苗	prM-E/NS1	ZIKV	临床一期	Inovio GeneOne
IgEsig-prM-E-LNP	mRNA疫苗	prM-E	ZIKV	动物实验	[188]

候选因子	蚊虫媒介	对病毒感染的影响	机制与功能
α-葡萄糖苷酶	埃及伊蚊	抑制DENV-2的复制和传播	α-葡萄糖苷酶抑制剂能够抑制内质网出芽病毒的复制^[211]；这种酶在蚊子中肠细胞被DENV-2的感染中起作用^[212]
羧肽酶B-1（CPB-1）	埃及伊蚊	抑制蚊子中的DENV-2感染	与沉积在内质网腔内膜上的E蛋白结合并抑制DENV-2的RNA封装，从而抑制病毒在内质网上的出芽，并可能干扰未成熟病毒向高尔基体网络的运输^[210,213]
富含半胱氨酸的毒液蛋白	埃及伊蚊	登革病毒感染蚊虫的过程中需要这种蛋白	与抑制素蛋白相互作用；登革病毒对埃及伊蚊的感染需要这种蛋白质^[99]
糖蛋白（Glycoproteins）	蚊虫	阻断目标病毒	潜在的普遍疾病传播阻断目标^[214]
热休克蛋白60（Hsp60）	埃及伊蚊	Hsp60 蛋白影响DENV-2对蚊虫的感染	感染了DENV-2的埃及伊蚊中Hsp60的水平上调^[212]
蚊子半乳糖特异性C型凝集素-1（mosGCTL-1）	埃及伊蚊、致倦库蚊	抑制蚊子中西尼罗病毒的感染	参与西尼罗病毒对细胞的附着过程，免疫沉淀实验表明，该蛋白与西尼罗病毒颗粒相互作用并结合^[94]
蚊子半乳糖特异性C型凝集素-3（mosGCTL-3）	埃及伊蚊	抑制蚊子中登革病毒的感染	通过与登革病毒E蛋白相互作用调节病毒进入细胞的过程^[95]
蚊子半乳糖特异性C型凝集素-7（mosGCTL-7）	埃及伊蚊	mosGCTL-7介导乙型脑炎病毒感染	mosGCTL-7在乙型脑炎病毒E蛋白的N154位点与N-聚糖结合。病毒感染需要mosGCTL-7能够识别病毒N-聚糖^[215]
蚊子半乳糖特异性C型凝集素-15, 19, 20, 22, 23, 24, 26, 32	埃及伊蚊	抑制蚊子中登革病毒的感染	通过与登革病毒E蛋白相互作用调节病毒进入细胞的过程^[95]
蚊子蛋白酪氨酸磷酸酶-1 （mosPTP-1）	伊蚊、库蚊	mosPTP-1参与西尼罗病毒和乙型脑炎病毒的内吞作用	分泌蛋白mosGCTL-1通过与病毒相互作用并将其桥接至mosPTP-1细胞受体来增强西尼罗病毒感染^[216]；mosPTP-1可促进埃及伊蚊中的乙型脑炎病毒感染^[215]
唾液蛋白	埃及伊蚊	抑制或增强登革病毒感染	参考2.3.2节

候选因子	蚊虫媒介	对病毒感染的影响	机制与功能
α-葡萄糖苷酶	埃及伊蚊	抑制DENV-2的复制和传播	α-葡萄糖苷酶抑制剂能够抑制内质网出芽病毒的复制^[211]；这种酶在蚊子中肠细胞被DENV-2的感染中起作用^[212]
羧肽酶B-1（CPB-1）	埃及伊蚊	抑制蚊子中的DENV-2感染	与沉积在内质网腔内膜上的E蛋白结合并抑制DENV-2的RNA封装，从而抑制病毒在内质网上的出芽，并可能干扰未成熟病毒向高尔基体网络的运输^[210,213]
富含半胱氨酸的毒液蛋白	埃及伊蚊	登革病毒感染蚊虫的过程中需要这种蛋白	与抑制素蛋白相互作用；登革病毒对埃及伊蚊的感染需要这种蛋白质^[99]
糖蛋白（Glycoproteins）	蚊虫	阻断目标病毒	潜在的普遍疾病传播阻断目标^[214]
热休克蛋白60（Hsp60）	埃及伊蚊	Hsp60 蛋白影响DENV-2对蚊虫的感染	感染了DENV-2的埃及伊蚊中Hsp60的水平上调^[212]
蚊子半乳糖特异性C型凝集素-1（mosGCTL-1）	埃及伊蚊、致倦库蚊	抑制蚊子中西尼罗病毒的感染	参与西尼罗病毒对细胞的附着过程，免疫沉淀实验表明，该蛋白与西尼罗病毒颗粒相互作用并结合^[94]
蚊子半乳糖特异性C型凝集素-3（mosGCTL-3）	埃及伊蚊	抑制蚊子中登革病毒的感染	通过与登革病毒E蛋白相互作用调节病毒进入细胞的过程^[95]
蚊子半乳糖特异性C型凝集素-7（mosGCTL-7）	埃及伊蚊	mosGCTL-7介导乙型脑炎病毒感染	mosGCTL-7在乙型脑炎病毒E蛋白的N154位点与N-聚糖结合。病毒感染需要mosGCTL-7能够识别病毒N-聚糖^[215]
蚊子半乳糖特异性C型凝集素-15, 19, 20, 22, 23, 24, 26, 32	埃及伊蚊	抑制蚊子中登革病毒的感染	通过与登革病毒E蛋白相互作用调节病毒进入细胞的过程^[95]
蚊子蛋白酪氨酸磷酸酶-1 （mosPTP-1）	伊蚊、库蚊	mosPTP-1参与西尼罗病毒和乙型脑炎病毒的内吞作用	分泌蛋白mosGCTL-1通过与病毒相互作用并将其桥接至mosPTP-1细胞受体来增强西尼罗病毒感染^[216]；mosPTP-1可促进埃及伊蚊中的乙型脑炎病毒感染^[215]
唾液蛋白	埃及伊蚊	抑制或增强登革病毒感染	参考2.3.2节