Kuno G
Division of Vector-Borne Infectious Diseases, National Center for Infectious Diseases, Centers for Disease Control and Prevention, Fort Collins, CO 80522-2087, USA.
J Virol Methods. 1998 May;72(1):27-41. doi: 10.1016/s0166-0934(98)00003-2.
A selected number of PCR protocols were evaluated to determine if they could serve as a universal protocol for detecting and identifying all arboviruses. In this study, four parameters that affect the efficacy of RT-PCR (RNA extraction method, choice of reverse transcriptase, choice of DNA polymerase and thermocycling program) were evaluated in combination. The most optimal combination of those parameters employed use of silica gel membrane spin column, RAV-2 reverse transcriptase, Tth DNA polymerase, and a simple modification of a published thermocycling program. By this modified protocol, viral RNA could be amplified satisfactorily with more than 50 pairs of primers designed for diagnosis of arboviruses representing five families. The sensitivity and specificity obtained by this universal protocol were comparable to those obtained by the original protocol for each primer pair tested; and for some primers, improved sensitivity was observed. It was also found that a simple modification of a suggested protocol of a commercial RT-PCR kit could produce nearly identical results and serve as another universal protocol. With the use of a universal diagnostic reverse transcriptase-polymerase chain reaction (RT-PCR) protocol, simultaneous screening of clinical or biological specimens against a large number of RNA viruses belonging to many families can be performed more efficiently for etiologic determination in the situations complicated by the difficulty of differential diagnosis. Furthermore, such a universal protocol facilitates reducing the cost of PCR-based diagnostic operation and standardizing the qualities of PCR-based diagnosis within an institution or among collaborating institutions. A logical strategy is to conduct diagnosis in two stages by using broadly group-reactive primers in the first stage to narrow the range of possible etiologic agents and using virus-specific primers in the second stage for identification. Before such a strategy is employed, however, more group-reactive primers for a large number of arboviruses, for which no such primers currently exist, must be made available. Furthermore, the best pair or pairs of primers need to be selected for each virus for the second stage of the strategy.
对选定的一些聚合酶链式反应(PCR)方案进行了评估,以确定它们是否可作为检测和鉴定所有虫媒病毒的通用方案。在本研究中,对影响逆转录聚合酶链式反应(RT-PCR)效率的四个参数(RNA提取方法、逆转录酶的选择、DNA聚合酶的选择和热循环程序)进行了综合评估。这些参数的最佳组合采用硅胶膜离心柱、禽成髓细胞瘤病毒2型(RAV-2)逆转录酶、嗜热栖热菌DNA聚合酶(Tth DNA聚合酶),并对已发表的热循环程序进行了简单修改。通过这种改良方案,使用为诊断代表五个科的虫媒病毒而设计的50多对引物,可以令人满意地扩增病毒RNA。该通用方案获得的灵敏度和特异性与测试的每个引物对的原始方案相当;对于一些引物,还观察到灵敏度有所提高。还发现,对商业RT-PCR试剂盒建议方案进行简单修改可产生几乎相同的结果,并可作为另一种通用方案。使用通用诊断逆转录聚合酶链式反应(RT-PCR)方案,可以在鉴别诊断困难的复杂情况下,更有效地同时针对大量属于多个科的RNA病毒对临床或生物标本进行筛查,以确定病因。此外,这样的通用方案有助于降低基于PCR的诊断操作成本,并使机构内部或合作机构之间基于PCR的诊断质量标准化。一种合理的策略是分两个阶段进行诊断,第一阶段使用广泛的组反应性引物来缩小可能的病原体范围,第二阶段使用病毒特异性引物进行鉴定。然而,在采用这种策略之前,必须提供更多针对大量目前尚无此类引物的虫媒病毒的组反应性引物。此外,需要为该策略的第二阶段为每种病毒选择最佳的一对或多对引物。