Identification of an overabundant cholesterol precursor in hepatitis B virus replicating cells by untargeted lipid metabolite profiling.
Identification of an overabundant cholesterol precursor in hepatitis B virus replicating cells by untargeted lipid metabolite profiling.
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DOI：
10.1021/ja809949r
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发表时间：
2009-04-15
影响因子：
15
通讯作者：
Yang PL
中科院分区：
文献类型：
--
作者：
Rodgers MA;Saghatelian A;Yang PL
病毒依赖于宿主脂质代谢途径进行成功复制，并且这些途径作为抗病毒药物发现的新型治疗靶点越来越受到关注。尽管如此，对病毒感染对细胞脂质代谢的影响知之甚少，病毒利用的特定脂质代谢物尚未被研究。我们应用基于液相色谱-质谱（LC-MS）的发现代谢物谱（DEEP）来鉴定脂质代谢物，其稳态丰度因主要人类病原体B型肝炎病毒（HBV）的复制而显著改变。研究表明，尽管主要脂质类别不受HBV影响，但367 m/z的离子在HBV+细胞中过量18倍。如离子碎裂质谱法和与标准品共进样所示，该离子的鉴别为7-脱氢胆固醇（7-DHC），是胆固醇的直接脱氢前体。虽然胆固醇先前已被证明是许多病毒复制所必需的，但这是第一次表明病毒复制与7-DHC的选择性积累有关。迄今为止，大多数病毒学研究都依赖于耗尽所有甾醇的方法，并排除观察到病毒病原体对甾醇利用的任何选择性。我们的研究表明，HBV可以选择性地利用7-DHC与其他甾醇和提示实验调查的功能意义，这种富集和阐明的机制，它是实现。这些结果还突出了作为鉴定病毒感染的关键代谢物的方法的ESTA的价值。
Viruses rely upon host lipid metabolic pathways for successful replication, and there is increasing interest in these pathways as novel therapeutic targets for antiviral drug discovery. Despite this, relatively little is known about the impact of viral infection on cellular lipid metabolism, and the specific lipid metabolites utilized by viruses have not yet been examined. We have applied liquid chromatography-mass spectroscopy (LC-MS) based discovery metabolite profiling (DMP) to identify lipid metabolites whose steady-state abundance is significantly altered by replication of hepatitis B virus (HBV), a major human pathogen. DMP indicated that although major lipid classes were unaffected by HBV, an ion of 367 m/z was overabundant in HBV+ cells by 18-fold. As shown by ion fragmentation mass spectrometry and co-injection with standard, the identity of this ion is 7-dehydrocholesterol (7-DHC), an immediate dehydrogenated precursor to cholesterol. While cholesterol has previously been demonstrated to be essential in the replication of many viruses, this is the first to show that viral replication is associated with the selective accumulation of 7-DHC. Most virological studies to date have relied upon methods that deplete all sterols and preclude the observation of any selectivity in sterol utilization by viral pathogens. Our study suggests that HBV may selectively utilize 7-DHC versus other sterols and prompts experiments investigating the functional significance of this enrichment and the elucidation of the mechanism by which it is achieved. The results also highlight the value of DMP as a method for identifying critical metabolites for viral infection.
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影响因子：
25.7
作者：
Sun, Dianxing;Nassal, Michael
通讯作者：
Nassal, Michael
DOI：
10.1007/s00249-007-0201-z
发表时间：
2007-11
期刊：
European biophysics journal : EBJ
影响因子：
--
作者：
Teissier E;Pécheur EI
通讯作者：
Pécheur EI
影响因子：
5.4
作者：
Kapadia, Sharookh B.;Barth, Heidi;Chisari, Francis V.
通讯作者：
Chisari, Francis V.
影响因子：
2.9
作者：
Shrivastava, Sandeep;Paila, Yamuna Devi;Chattopadhyay, Amitabha
通讯作者：
Chattopadhyay, Amitabha
影响因子：
3.4
作者：
Bremer, Corinna M.;Bung, Christiane;Glebe, Dieter
通讯作者：
Glebe, Dieter