Tanner Lukas Bahati, Chng Charmaine, Guan Xue Li, Lei Zhengdeng, Rozen Steven G, Wenk Markus R
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456 NUS Graduate School for Integrative Sciences and Engineering (NGS), National University of Singapore, Singapore 117456.
Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117456.
J Lipid Res. 2014 Jul;55(7):1357-65. doi: 10.1194/jlr.M049148. Epub 2014 May 27.
Influenza virus acquires a host-derived lipid envelope during budding, yet a convergent view on the role of host lipid metabolism during infection is lacking. Using a mass spectrometry-based lipidomics approach, we provide a systems-scale perspective on membrane lipid dynamics of infected human lung epithelial cells and purified influenza virions. We reveal enrichment of the minor peroxisome-derived ether-linked phosphatidylcholines relative to bulk ester-linked phosphatidylcholines in virions as a unique pathogenicity-dependent signature for influenza not found in other enveloped viruses. Strikingly, pharmacological and genetic interference with peroxisomal and ether lipid metabolism impaired influenza virus production. Further integration of our lipidomics results with published genomics and proteomics data corroborated altered peroxisomal lipid metabolism as a hallmark of influenza virus infection in vitro and in vivo. Influenza virus may therefore tailor peroxisomal and particularly ether lipid metabolism for efficient replication.
流感病毒在出芽过程中获得宿主来源的脂质包膜，但目前缺乏关于宿主脂质代谢在感染过程中作用的统一观点。我们采用基于质谱的脂质组学方法，从系统层面观察了受感染的人肺上皮细胞和纯化流感病毒颗粒的膜脂动态变化。我们发现，相对于大量酯连接的磷脂酰胆碱，病毒颗粒中源自过氧化物酶体的少量醚连接磷脂酰胆碱有所富集，这是流感病毒特有的致病性相关特征，在其他包膜病毒中未发现。引人注目的是，对过氧化物酶体和醚脂代谢的药理和基因干扰会损害流感病毒的产生。我们将脂质组学结果与已发表的基因组学和蛋白质组学数据进一步整合，证实过氧化物酶体脂质代谢改变是流感病毒在体外和体内感染的一个标志。因此，流感病毒可能会调整过氧化物酶体尤其是醚脂代谢以实现高效复制。
