Reeves Matthew B, Davies Andrew A, McSharry Brian P, Wilkinson Gavin W, Sinclair John H
Department of Medicine, University of Cambridge, Addenbrooke's Hospital, Hills Road, Cambridge, CB2 2QQ, UK.
Science. 2007 Jun 1;316(5829):1345-8. doi: 10.1126/science.1142984.
Human cytomegalovirus infection perturbs multiple cellular processes that could promote the release of proapoptotic stimuli. Consequently, it encodes mechanisms to prevent cell death during infection. Using rotenone, a potent inhibitor of the mitochondrial enzyme complex I (reduced nicotinamide adenine dinucleotide-ubiquinone oxido-reductase), we found that human cytomegalovirus infection protected cells from rotenone-induced apoptosis, a protection mediated by a 2.7-kilobase virally encoded RNA (beta2.7). During infection, beta2.7 RNA interacted with complex I and prevented the relocalization of the essential subunit genes associated with retinoid/interferon-induced mortality-19, in response to apoptotic stimuli. This interaction, which is important for stabilizing the mitochondrial membrane potential, resulted in continued adenosine triphosphate production, which is critical for the successful completion of the virus' life cycle. Complex I targeting by a viral RNA represents a refined strategy to modulate the metabolic viability of the infected host cell.
人巨细胞病毒感染会扰乱多个细胞过程，这些过程可能会促进促凋亡刺激的释放。因此，它编码了在感染期间防止细胞死亡的机制。使用鱼藤酮，一种线粒体酶复合物I（还原型烟酰胺腺嘌呤二核苷酸-泛醌氧化还原酶）的有效抑制剂，我们发现人巨细胞病毒感染可保护细胞免受鱼藤酮诱导的凋亡，这种保护作用由一种2.7千碱基的病毒编码RNA（β2.7）介导。在感染期间，β2.7 RNA与复合物I相互作用，并防止视黄酸/干扰素诱导的死亡率-19相关的必需亚基基因响应凋亡刺激而重新定位。这种相互作用对于稳定线粒体膜电位很重要，导致三磷酸腺苷持续产生，这对于病毒生命周期的成功完成至关重要。病毒RNA靶向复合物I代表了一种调节受感染宿主细胞代谢活力的精细策略。
