Role of Oxysterol Binding Protein in Hepatitis C Virus infection
Role of Oxysterol Binding Protein in Hepatitis C Virus infection
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DOI：
10.1128/jvi.00958-09
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发表时间：
2009-09-15
影响因子：
5.4
通讯作者：
Siddiqui, Aleem
中科院分区：
文献类型：
--
作者：
Amako, Yutaka;Sarkeshik, Ali;Siddiqui, Aleem
丙型肝炎病毒（HCV）RNA基因组在内质网延伸的修饰膜结构中的核糖核蛋白（RNP）复合物内复制。对HCV RNP复合物的蛋白质组学分析揭示了氧固醇结合蛋白（OSBP）作为这些复合物的组分之一的关联。OSBP与HCV NS 5A蛋白的N-末端结构域I相互作用，并与NS 5A共定位于高尔基室。OSBP特异性短发夹RNA部分下调OSBP表达导致培养上清液中HCV颗粒释放减少，对病毒RNA复制影响不大。位于OSBP N-末端区域的pleckstrin同源（PH）结构域将该蛋白质靶向高尔基体。OSBP缺失突变的PH（Δ PH）域未能定位到高尔基体和抑制HCV颗粒的释放。这些研究表明OSBP在HCV成熟过程中可能发挥功能性作用。
Hepatitis C virus (HCV) RNA genome replicates within the ribonucleoprotein (RNP) complex in the modified membranous structures extended from endoplasmic reticulum. A proteomic analysis of HCV RNP complexes revealed the association of oxysterol binding protein (OSBP) as one of the components of these complexes. OSBP interacted with the N-terminal domain I of the HCV NS5A protein and colocalized to the Golgi compartment with NS5A. An OSBP-specific short hairpin RNA that partially downregulated OSBP expression resulted in a decrease of the HCV particle release in culture supernatant with little effect on viral RNA replication. The pleckstrin homology (PH) domain located in the N-terminal region of OSBP targeted this protein to the Golgi apparatus. OSBP deletion mutation in the PH (Delta PH) domain failed to localize to the Golgi apparatus and inhibited the HCV particle release. These studies suggest a possible functional role of OSBP in the HCV maturation process.