Viruses 2012, 4(10), 2340-2358; doi:10.3390/v4102340
Review

Phosphoinositides in the Hepatitis C Virus Life Cycle

1,2email, 2email and 2,* email
Received: 4 September 2012; in revised form: 5 October 2012 / Accepted: 9 October 2012 / Published: 19 October 2012
(This article belongs to the Special Issue Hepatitis C Pathology)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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 generation of ER-specific PI4P pools. Inhibition of PI4KIIIα abrogates HCV replication. PI4P, the most abundant phosphoinositide, predominantly localizes to the Golgi and plays central roles in Golgi secretory functions by recruiting effector proteins involved in transport vesicle generation. The PI4P effector proteins also include the lipid-transfer and structural proteins such as ceramide transfer protein (CERT), oxysterol binding protein (OSBP) and Golgi phosphoprotein 3 (GOLPH3) that help maintain Golgi-membrane composition and structure. Depletion of Golgi-specific PI4P pools by silencing PI4KIIIβ, expression of dominant negative CERT and OSBP mutants, or silencing GOLPH3 perturb HCV secretion. In this review we highlight the role of PIPs and specifically PI4P in the HCV life cycle.
Keywords: HCV; hepatitis C; PI4P; phosphoinositides; PI4KIIIα; PI4KIIIβ
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MDPI and ACS Style

Bishé, B.; Syed, G.; Siddiqui, A. Phosphoinositides in the Hepatitis C Virus Life Cycle. Viruses 2012, 4, 2340-2358.

AMA Style

Bishé B, Syed G, Siddiqui A. Phosphoinositides in the Hepatitis C Virus Life Cycle. Viruses. 2012; 4(10):2340-2358.

Chicago/Turabian Style

Bishé, Bryan; Syed, Gulam; Siddiqui, Aleem. 2012. "Phosphoinositides in the Hepatitis C Virus Life Cycle." Viruses 4, no. 10: 2340-2358.


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