源自新大陆寨卡病毒感染性克隆的重组病毒的开发与特性分析
Development and Characterization of Recombinant Virus Generated from a New World Zika Virus Infectious Clone.
作者信息
Weger-Lucarelli James, Duggal Nisha K, Bullard-Feibelman Kristen, Veselinovic Milena, Romo Hannah, Nguyen Chilinh, Rückert Claudia, Brault Aaron C, Bowen Richard A, Stenglein Mark, Geiss Brian J, Ebel Gregory D
机构信息
Department of Microbiology, Immunology, and Pathology, Colorado State University, Fort Collins, Colorado, USA.
Division of Vector-Borne Diseases, Centers for Disease Control and Prevention, Fort Collins, Colorado, USA.
出版信息
J Virol. 2016 Dec 16;91(1). doi: 10.1128/JVI.01765-16. Print 2017 Jan 1.
UNLABELLED
Zika virus (ZIKV; family Flaviviridae, genus Flavivirus) is a rapidly expanding global pathogen that has been associated with severe clinical manifestations, including devastating neurological disease in infants. There are currently no molecular clones of a New World ZIKV available that lack significant attenuation, hindering progress toward understanding determinants of transmission and pathogenesis. Here we report the development and characterization of a novel ZIKV reverse genetics system based on a 2015 isolate from Puerto Rico (PRVABC59). We generated a two-plasmid infectious clone system from which infectious virus was rescued that replicates in human and mosquito cells with growth kinetics representative of wild-type ZIKV. Infectious clone-derived virus initiated infection and transmission rates in Aedes aegypti mosquitoes comparable to those of the primary isolate and displayed similar pathogenesis in AG129 mice. This infectious clone system provides a valuable resource to the research community to explore ZIKV molecular biology, vaccine development, antiviral development, diagnostics, vector competence, and disease pathogenesis.
IMPORTANCE
ZIKV is a rapidly spreading mosquito-borne pathogen that has been linked to Guillain-Barré syndrome in adults and congenital microcephaly in developing fetuses and infants. ZIKV can also be sexually transmitted. The viral molecular determinants of any of these phenotypes are not well understood. There is no reverse genetics system available for the current epidemic virus that will allow researchers to study ZIKV immunity, develop novel vaccines, or develop antiviral drugs. Here we provide a novel infectious clone system generated from a recent ZIKV isolated from a patient infected in Puerto Rico. This infectious clone produces virus with in vitro and in vivo characteristics similar to those of the primary isolate, providing a critical tool to study ZIKV infection and disease.
未标记
寨卡病毒（ZIKV；黄病毒科黄病毒属）是一种在全球迅速传播的病原体，与严重的临床表现相关，包括婴儿毁灭性的神经系统疾病。目前尚无缺乏显著减毒的新大陆寨卡病毒分子克隆，这阻碍了对传播和发病机制决定因素的理解进展。在此，我们报告了基于2015年从波多黎各分离株（PRVABC59）开发和表征的新型寨卡病毒反向遗传学系统。我们构建了一个双质粒感染性克隆系统，从中拯救出的感染性病毒可在人细胞和蚊细胞中复制，其生长动力学代表野生型寨卡病毒。感染性克隆衍生的病毒在埃及伊蚊中的感染和传播率与原始分离株相当，并且在AG129小鼠中表现出相似的发病机制。这个感染性克隆系统为研究界提供了一个宝贵资源，用于探索寨卡病毒分子生物学、疫苗开发、抗病毒药物开发、诊断、媒介能力和疾病发病机制。
重要性
寨卡病毒是一种迅速传播的蚊媒病原体，与成人吉兰 - 巴雷综合征以及发育中的胎儿和婴儿先天性小头畸形有关。寨卡病毒也可通过性传播。这些表型中任何一种的病毒分子决定因素都尚未完全了解。目前流行的病毒没有可用的反向遗传学系统，这使得研究人员无法研究寨卡病毒免疫、开发新型疫苗或开发抗病毒药物。在此，我们提供了一种由最近从波多黎各感染患者分离的寨卡病毒产生的新型感染性克隆系统。这种感染性克隆产生的病毒在体外和体内的特征与原始分离株相似，为研究寨卡病毒感染和疾病提供了关键工具。
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