Chiang Cheng-Feng, Albariňo Cesar G, Lo Michael K, Spiropoulou Christina F
Viral Special Pathogens Branch, Division of High-Consequence Pathogens and Pathology, Centers for Disease Control and Prevention, Atlanta, Georgia, United States of America.
PLoS One. 2014 Jun 12;9(6):e99764. doi: 10.1371/journal.pone.0099764. eCollection 2014.
Andes virus (ANDV) is the most common causative agent of hantavirus pulmonary syndrome (HPS) in the Americas, and is the only hantavirus associated with human-to-human transmission. Case fatality rates of ANDV-induced HPS are approximately 40%. There are currently no effective vaccines or antivirals against ANDV. Since HPS severity correlates with viral load, we tested small interfering RNA (siRNA) directed against ANDV genes as a potential antiviral strategy. We designed pools of 4 siRNAs targeting each of the ANDV genome segments (S, M, and L), and tested their efficacy in reducing viral replication in vitro. The siRNA pool targeting the S segment reduced viral transcription and replication in Vero-E6 cells more efficiently than those targeting the M and L segments. In contrast, siRNAs targeting the S, M, or L segment were similar in their ability to reduce viral replication in human lung microvascular endothelial cells. Importantly, these siRNAs inhibit ANDV replication even if given after infection. Taken together, our findings indicate that siRNAs targeting the ANDV genome efficiently inhibit ANDV replication, and show promise as a strategy for developing therapeutics against ANDV infection.
安第斯病毒（ANDV）是美洲汉坦病毒肺综合征（HPS）最常见的病原体，并且是唯一与人传人传播相关的汉坦病毒。ANDV诱发的HPS病死率约为40%。目前尚无针对ANDV的有效疫苗或抗病毒药物。由于HPS的严重程度与病毒载量相关，我们测试了针对ANDV基因的小干扰RNA（siRNA）作为一种潜在的抗病毒策略。我们设计了针对ANDV每个基因组片段（S、M和L）的4条siRNA池，并测试了它们在体外降低病毒复制的效果。与靶向M和L片段的siRNA池相比，靶向S片段的siRNA池在Vero-E6细胞中更有效地降低了病毒转录和复制。相比之下，靶向S、M或L片段的siRNA在降低人肺微血管内皮细胞中病毒复制的能力方面相似。重要的是，即使在感染后给予这些siRNA也能抑制ANDV复制。综上所述，我们的研究结果表明，靶向ANDV基因组的siRNA能有效抑制ANDV复制，并有望成为开发针对ANDV感染的治疗方法的一种策略。
