Wheeler Sarah S, Ball Cameron S, Langevin Stanley A, Fang Ying, Coffey Lark L, Meagher Robert J
University of California Davis, School of Veterinary Medicine, Department of Pathology, Microbiology and Immunology, Davis, California, United States of America.
Sandia National Laboratories, Biotechnology and Bioengineering Department, Livermore, California, United States of America.
PLoS One. 2016 Jan 25;11(1):e0147962. doi: 10.1371/journal.pone.0147962. eCollection 2016.
Collection of mosquitoes and testing for vector-borne viruses is a key surveillance activity that directly influences the vector control efforts of public health agencies, including determining when and where to apply insecticides. Vector control districts in California routinely monitor for three human pathogenic viruses including West Nile virus (WNV), Western equine encephalitis virus (WEEV), and St. Louis encephalitis virus (SLEV). Reverse transcription quantitative polymerase chain reaction (RT-qPCR) offers highly sensitive and specific detection of these three viruses in a single multiplex reaction, but this technique requires costly, specialized equipment that is generally only available in centralized public health laboratories. We report the use of reverse transcription loop-mediated isothermal amplification (RT-LAMP) to detect WNV, WEEV, and SLEV RNA extracted from pooled mosquito samples collected in California, including novel primer sets for specific detection of WEEV and SLEV, targeting the nonstructural protein 4 (nsP4) gene of WEEV and the 3' untranslated region (3'-UTR) of SLEV. Our WEEV and SLEV RT-LAMP primers allowed detection of <0.1 PFU/reaction of their respective targets in <30 minutes, and exhibited high specificity without cross reactivity when tested against a panel of alphaviruses and flaviviruses. Furthermore, the SLEV primers do not cross-react with WNV, despite both viruses being closely related members of the Japanese encephalitis virus complex. The SLEV and WEEV primers can also be combined in a single RT-LAMP reaction, with discrimination between amplicons by melt curve analysis. Although RT-qPCR is approximately one order of magnitude more sensitive than RT-LAMP for all three targets, the RT-LAMP technique is less instrumentally intensive than RT-qPCR and provides a more cost-effective method of vector-borne virus surveillance.
蚊子采集及媒介传播病毒检测是一项关键监测活动,直接影响公共卫生机构的病媒控制工作,包括确定何时何地使用杀虫剂。加利福尼亚州的病媒控制区定期监测三种人类致病病毒,包括西尼罗河病毒(WNV)、西部马脑炎病毒(WEEV)和圣路易斯脑炎病毒(SLEV)。逆转录定量聚合酶链反应(RT-qPCR)可在单一多重反应中对这三种病毒进行高度灵敏且特异的检测,但该技术需要昂贵的专用设备,而这种设备通常仅在集中的公共卫生实验室中才有。我们报告了使用逆转录环介导等温扩增(RT-LAMP)来检测从加利福尼亚州采集的混合蚊子样本中提取的WNV、WEEV和SLEV RNA,包括用于特异性检测WEEV和SLEV的新型引物组,其靶向WEEV的非结构蛋白4(nsP4)基因和SLEV的3'非翻译区(3'-UTR)。我们的WEEV和SLEV RT-LAMP引物能够在不到30分钟的时间内检测到各自靶标的<0.1 PFU/反应,并且在针对一组甲病毒和黄病毒进行测试时表现出高特异性,无交叉反应。此外,尽管SLEV和WNV都是日本脑炎病毒复合体的密切相关成员,但SLEV引物与WNV不发生交叉反应。SLEV和WEEV引物也可在单个RT-LAMP反应中组合,通过熔解曲线分析区分扩增子。尽管对于所有三个靶标,RT-qPCR的灵敏度比RT-LAMP高约一个数量级,但RT-LAMP技术比RT-qPCR对仪器的要求更低,并且提供了一种更具成本效益的媒介传播病毒监测方法。