PDF(Pubmed)
Abstract：
Lassa virus (LASV), a risk-group 4 pathogen, must be handled in biosafety level-4 (BSL-4) conditions, thereby limiting its research and antiviral development. Here, we developed a novel LASV reverse genetics system which, to our knowledge, is the first to study the complete LASV life cycle under BSL-2 conditions. Viral particles can be produced efficiently when LASV minigenomic RNA harbouring minimal viral cis-elements and reporter genes is transfected into a helper cell line stably expressing viral NP, GP, Z and L proteins. The resulting defective virions, named LASVmg, can propagate only in the helper cell line, providing a BSL-2 model to study the complete LASV life cycle. Using this model, we found that a previously reported cellular receptor α-dystroglycan is dispensable for LASVmg infection. Furthermore, we showed that ribavirin can inhibit LASVmg infection by inducing viral mutations. This new BSL-2 system should facilitate studying the LASV life cycle and screening antivirals.
摘要：
拉沙病毒(LASV)风险组4病原体，必须在生物安全4级(BSL-4)条件下处理，从而限制了其研究和抗病毒的发展。这里,我们开发了一个新的LASV反向遗传学系统，根据我们的知识，首次在BSL-2条件下研究完整的LASV生命周期。当携带最小病毒顺式元件和报告基因的LASV小基因组RNA被转染到稳定表达病毒NP的辅助细胞系中时，可以有效地产生病毒颗粒。GP,Z和L蛋白。由此产生的有缺陷的病毒体，名叫LASVmg,只能在辅助细胞系中繁殖，提供BSL-2模型来研究完整的LASV生命周期。使用这个模型，我们发现，以前报道的细胞受体α-营养不良聚糖对于LASVmg感染是不必要的。此外，我们表明利巴韦林可以通过诱导病毒突变来抑制LASVmg感染。这种新的BSL-2系统应该有助于研究LASV生命周期和筛选抗病毒药物。
