Virology Division, Defence Research Development Establishment, Jhansi Road, Gwalior, 474002, India.
Vertox Division, Defence Research Development Establishment, Jhansi Road, Gwalior, 474002, India.
Sci Rep. 2020 Jul 15;10(1):11651. doi: 10.1038/s41598-020-68469-2.
The molecular detection system has evolved over last two decades and is rapidly replacing the conventional confirmatory techniques in diagnostic virology. However the major limitation in implementation of available molecular detection assays is the non availability of field deployable nucleic acid isolation platform coupled with gene amplification technique. The rapid and early molecular detection is crucial for employing effective measure against many viral infections. The re-emergence of chikungunya virus (CHIKV) has led to epidemics since 2004 in several parts of the world including India. The main association of CHIKV with severe arthritis and long-lasting arthralgia and closely mimics symptoms of Dengue and Zika virus infection requiring laboratory confirmation. In this study, a simple magnetic bead based ribonucleic acid extraction method was optimized, which was coupled with isothermal polymerase spiral reaction (PSR) technique for early and rapid detection. Subsequently, the polymerase spiral reaction reagents were converted to dry down format that led to a rapid user friendly field compatible sample processing to answer method for rapid and onsite detection of Chikungunya virus. Both the methods were evaluated with a panel of clinical samples. The sensitivity of the assays were compared with available commercial viral RNA extraction platform and qRT-PCR. The in-house nucleic acid extraction system based on magnetic bead followed by dry down RT-Polymerase Spiral Reaction assay was found to be highly sensitive with 10 copies of RNA as limit of detection in CHIKV clinical specimens. With respect to other closely related viruses no cross reactivity was observed. This novel methodology has the potential to revolutionize the diagnosis of infectious agents in resource limited settings around the world.
分子检测系统在过去二十年中不断发展,正在迅速取代诊断病毒学中的传统确认技术。然而,在实施现有分子检测方法时的主要限制是缺乏可现场部署的核酸分离平台以及基因扩增技术。快速和早期的分子检测对于采取有效措施应对许多病毒感染至关重要。基孔肯雅病毒 (CHIKV) 的再次出现导致自 2004 年以来在世界多个地区(包括印度)爆发了疫情。CHIKV 主要与严重关节炎和持久关节痛密切相关,其症状与登革热和寨卡病毒感染非常相似,需要实验室确认。在这项研究中,优化了一种简单的基于磁性珠的核糖核酸提取方法,该方法与等温聚合酶螺旋反应 (PSR) 技术相结合,用于早期和快速检测。随后,将聚合酶螺旋反应试剂转化为干燥格式,从而实现了快速用户友好的现场兼容样品处理,以满足快速和现场检测基孔肯雅病毒的方法。这两种方法都用一组临床样本进行了评估。与现有的商用病毒 RNA 提取平台和 qRT-PCR 相比,评估了这些方法的灵敏度。基于磁性珠的内部核酸提取系统和干燥 RT-聚合酶螺旋反应检测法发现对 CHIKV 临床标本具有高度的灵敏度,检测限为 10 个拷贝的 RNA。对于其他密切相关的病毒,没有观察到交叉反应。这种新方法有可能彻底改变全球资源有限环境中传染病原体的诊断。