phosphoinositides in the hepatitis c virus life cycle磷酸肌醇的丙型肝炎病毒的生命周期.pdfVIP

Viruses 2012, 4, 2340-2358; doi:10.3390/v4102340 OPEN ACCESS viruses ISSN 1999-4915 /journal/viruses Review Phosphoinositides in the Hepatitis C Virus Life Cycle Bryan Bishé 1,2, Gulam Syed 2 and Aleem Siddiqui 2,* 1 Division of Biological Sciences, University of California, San Diego. 9500 Gilman Dr., San Diego, CA, 92093, USA; E-Mail: bbishe@ 2 Division of Infectious Diseases, University of California, San Diego. 9500 Gilman Dr., San Diego, CA, 92093, USA; E-Mail: gsyed@ * Author to whom correspondence should be addressed; E-Mail: asiddiqui@; Tel.: +858-822-1750; Fax: +858-822-1749. Received: 4 September 2012; in revised form: 5 October 2012 / Accepted: 9 October 2012 / Published: 19 October 2012 Abstract: Eukaryotes possess seven different phosphoinositides (PIPs) that help form the unique signatures of various intracellular membranes. PIPs serve as docking sites for the recruitment of specific proteins to mediate membrane alterations and integrate various signaling cascades. The spatio-temporal regulation of PI kinases and phosphatases generates distinct intracellular hubs of PIP signaling. Hepatitis C virus (HCV), like other plus-strand RNA viruses, promotes the rearrangement of intracellular membranes to assemble viral replication complexes. HCV stimulates enrichment of phosphatidylinositol 4-phosphate (PI4P) pools near endoplasmic reticulum (ER) sites by activating PI4KIIIα, the kinase responsible for generat