Berger Kristi L, Randall Glenn
Department of Microbiology; The University of Chicago, Chicago, IL, USA.
Commun Integr Biol. 2009 Nov;2(6):471-3. doi: 10.4161/cib.2.6.9261.
Over 130 million people worldwide are chronically infected with hepatitis C virus (HCV). New antiviral treatment strategies are needed due to limitations with current therapy. The identification of cellular cofactors of infection has the potential to broadly expand our therapeutic targets. We recently reported an RNA interference screen of host membrane trafficking genes in HCV infection and replication and identified several cellular co-factors for viral replication. Phosphatidylinositol 4-kinase III alpha (PI4K-IIIalpha) was found to be essential for HCV replication. PI4K-IIIalpha co-localized with viral replication markers. Silencing of PI4K-IIIalpha by siRNAs prior to HCV infection prevented rearrangement of intracellular membranes associated with viral replication complexes, termed the membranous web. Our data suggest that PI4K-IIIalpha is involved in establishing HCV replication complexes, however the mechanism is unknown. From our analysis, along with several other studies that have identified cellular cofactors for HCV replication, we propose that PI4K-IIIalpha may nucleate replication complex formation by facilitating the interaction of viral and/or cellular proteins with cellular membrane-associated phospholipids.
全球超过1.3亿人长期感染丙型肝炎病毒（HCV）。由于目前治疗方法存在局限性，需要新的抗病毒治疗策略。鉴定感染的细胞辅助因子有可能广泛扩展我们的治疗靶点。我们最近报道了对HCV感染和复制过程中宿主膜运输基因的RNA干扰筛选，并鉴定了几种病毒复制的细胞辅助因子。发现磷脂酰肌醇4激酶IIIα（PI4K-IIIα）对HCV复制至关重要。PI4K-IIIα与病毒复制标志物共定位。在HCV感染前用小干扰RNA沉默PI4K-IIIα可防止与病毒复制复合物相关的细胞内膜重排，即膜性网。我们的数据表明PI4K-IIIα参与建立HCV复制复合物，但其机制尚不清楚。通过我们的分析，以及其他几项鉴定出HCV复制细胞辅助因子的研究，我们提出PI4K-IIIα可能通过促进病毒和/或细胞蛋白与细胞膜相关磷脂的相互作用来启动复制复合物的形成。
