Virusten replikaatiossa on tärkeä osa fosfatidyyli-inositoli-4- kinaasilla (PI4K) ja sen produktilla PI(4)P

 https://www.sciencedirect.com/science/article/pii/S0006295212005163?via%3Dihub#fig0005

 

Volume 84, Issue 11, 1 December 2012, Pages 1400-140

Commentary

The role of phosphatidylinositol 4-kinases and phosphatidylinositol 4-phosphate during viral replication

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Abstract

Phosphoinositides (PI) are phospholipids that mediate signaling cascades in the cell by binding to effector proteins. Reversible phosphorylation of the inositol ring at positions 3, 4 and 5 results in the synthesis of seven different phosphoinositides. Each phosphoinositide has a unique subcellular distribution with a predominant localization in subsets of membranes. These lipids play a major role in recruiting and regulating the function of proteins at membrane interfaces [1]. Several bacteria and viruses modulate and exploit the host PI metabolism to ensure efficient replication and survival. Here, we focus on the roles of cellular phosphatidylinositol 4-phosphate (PI4P) and phosphatidylinositol 4-kinases (PI4Ks) during the replication cycle of various viruses. It has been well documented that phosphatidylinositol 4-kinase IIIβ (PI4KIIIβ, EC 2.7.1.67) is indispensable for viral RNA replication of several picornaviruses. Two recruitment strategies were reported: (i) binding and modulation of GBF1/Arf1 to enhance recruitment of PI4KIIIβ and (ii) interaction with ACBD3 for recruitment of PI4KIIIβ. PI4KIII has also been demonstrated to be crucial for hepatitis C virus (HCV) replication. PI4KIII appears to be directly recruited and activated by HCV NS5A protein to the replication complexes. In contrast to picornaviruses, it is still debated whether the α or the β isoform is the most important. PI4KIII can be explored as a target for inhibition of viral replication. The challenge will be to develop highly selective inhibitors for PI4KIIIα and/or β and to avoid off-target toxicity.

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 Various viruses have an impact on the host's lipid metabolism, lipid/membrane transport and lipid mediated signal transduction. A key class of lipids involved in these cellular processes is the class of phosphoinositides (PIs). Phosphatidylinositol (PtdIns) is the basic scaffold of the PIs (Fig. 1).