Albulescu Lucian, Wubbolts Richard, van Kuppeveld Frank J M, Strating Jeroen R P M
Virology Division, Department of Infectious Diseases and Immunology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Department of Biochemistry and Cell Biology, Faculty of Veterinary Medicine, Utrecht University, Utrecht, The Netherlands.
Cell Microbiol. 2015 Aug;17(8):1144-56. doi: 10.1111/cmi.12425. Epub 2015 Mar 10.
Picornaviruses are a family of positive-strand RNA viruses that includes important human and animal pathogens. Upon infection, picornaviruses induce an extensive remodelling of host cell membranes into replication organelles (ROs), which is critical for replication. Membrane lipids and lipid remodelling processes are at the base of RO formation, yet their involvement remains largely obscure. Recently, phosphatidylinositol-4-phosphate was the first lipid discovered to be important for the replication of a number of picornaviruses. Here, we investigate the role of the lipid cholesterol in picornavirus replication. We show that two picornaviruses from distinct genera that rely on different host factors for replication, namely the enterovirus coxsackievirus B3 (CVB3) and the cardiovirus encephalomyocarditis virus (EMCV), both recruited cholesterol to their ROs. Although CVB3 and EMCV both required cholesterol for efficient genome replication, the viruses appeared to rely on different cellular cholesterol pools. Treatments that altered the distribution of endosomal cholesterol inhibited replication of both CVB3 and EMCV, showing the importance of endosomal cholesterol shuttling for the replication of these viruses. Summarizing, we here demonstrate the importance of cholesterol homeostasis for efficient replication of CVB3 and EMCV.
小核糖核酸病毒是一类正链RNA病毒，其中包括重要的人类和动物病原体。感染后，小核糖核酸病毒会诱导宿主细胞膜广泛重塑为复制细胞器（ROs），这对病毒复制至关重要。膜脂和脂质重塑过程是RO形成的基础，但其具体作用仍 largely obscure。最近，磷脂酰肌醇-4-磷酸是首个被发现对多种小核糖核酸病毒复制重要的脂质。在此，我们研究脂质胆固醇在小核糖核酸病毒复制中的作用。我们发现，来自不同属的两种小核糖核酸病毒，即依赖不同宿主因子进行复制的肠道病毒柯萨奇病毒B3（CVB3）和心肌炎病毒脑心肌炎病毒（EMCV），都会将胆固醇募集到它们的ROs中。虽然CVB3和EMCV高效基因组复制都需要胆固醇，但这两种病毒似乎依赖不同的细胞胆固醇池。改变内体胆固醇分布的处理会抑制CVB3和EMCV的复制，表明内体胆固醇穿梭对这些病毒复制的重要性。总之，我们在此证明了胆固醇稳态对CVB3和EMCV高效复制的重要性。
