合成生物学 ›› 2023, Vol. 4 ›› Issue (2): 347-372.DOI: 10.12211/2096-8280.2022-069
余茜1, 刘建英2, 程功1,2
收稿日期:
2022-12-06
修回日期:
2023-01-16
出版日期:
2023-04-30
发布日期:
2023-04-27
通讯作者:
程功
作者简介:
基金资助:
Xi YU1, Jianying LIU2, Gong CHENG1,2
Received:
2022-12-06
Revised:
2023-01-16
Online:
2023-04-30
Published:
2023-04-27
Contact:
Gong CHENG
摘要:
蚊媒病毒可通过蚊虫叮咬在宿主和蚊虫媒介之间传播循环。由蚊媒传播的病毒达数百种之多,每年可造成数亿人感染,这些病毒感染可引起严重的人类疾病,如出血热、关节炎、脑炎和脑膜炎等,严重者可导致死亡。蚊媒病毒大部分为RNA病毒,其中黄病毒科的蚊媒病毒流行最为广泛,包括登革病毒、寨卡病毒、黄热病毒、乙型脑炎病毒和西尼罗病毒等。目前虽然已有针对少数蚊媒黄病毒的有效疫苗,例如预防黄热病病毒和乙型脑炎病毒的疫苗,但仍然没有针对大多数蚊媒黄病毒的有效预防性疫苗和抗病毒疗法。因此,全面了解蚊媒黄病毒在脊椎动物宿主与蚊虫之间的感染与传播的机制,可能为抗蚊媒黄病毒的疫苗与药物研发提供新的思路与目标,从而使我们能够更有效地预测和控制蚊媒黄病毒在自然界传播和流行,为应对蚊媒黄病毒造成的公共卫生威胁提供新的解决方案。本文首先描述了蚊媒黄病毒的生物学特性和流行病学特性,接下来介绍了蚊媒黄病毒的传播途径与媒介模型,并进一步全面总结了目前对蚊媒黄病毒在宿主和媒介之间传播机制及病毒在蚊虫媒介中的感染机制的研究,同时针对蚊媒黄病毒的新型疫苗研发和药物筛选策略,对未来针对蚊媒黄病毒的机制研究与抗病毒策略开发进行了展望。
中图分类号:
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.
Xi YU, Jianying LIU, Gong CHENG. Research progress in mosquito-borne flaviviruses transmission and the development of vaccines and drugs[J]. Synthetic Biology Journal, 2023, 4(2): 347-372.
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 | [ |
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 | [ |
DENV-VLP | VLPs | prM-E | DENV 1~4 | 临床前 | [ |
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 | [ |
表1 针对蚊媒黄病毒的预防性疫苗
Table 1 Preventive vaccines against mosquito-borne flavivirus
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 | [ |
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 | [ |
DENV-VLP | VLPs | prM-E | DENV 1~4 | 临床前 | [ |
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 | [ |
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[ |
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[ |
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[ |
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[ |
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[ |
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[ |
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[ |
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[ |
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[ |
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[ |
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 |
表2 蚊媒黄病毒传播阻断疫苗开发的潜在候选因子
Table 2 Candidates of transmission-blocking vaccines for mosquito-borne flavivirus
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[ |
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[ |
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[ |
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[ |
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[ |
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[ |
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[ |
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[ |
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[ |
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[ |
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 |
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