Molecular mechanisms of PI4K regulation and their involvement in viral replication

Lipid phosphoinositides are master signaling molecules in eukaryotic cells and key markers of organelle identity. Because of these important roles, the kinases and phosphatases that generate phosphoinositides must be tightly regulated. Viruses can manipulate this regulation, with the Type III phosph...

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Bibliographic Details
Published in:Traffic (Copenhagen, Denmark) Denmark), 2023-03, Vol.24 (3), p.131-145
Main Authors: McPhail, Jacob A., Burke, John E.
Format: Article
Language:English
Subjects:
1-Phosphatidylinositol 4-Kinase - metabolism
ACBD3
Arf1
ARMH3
c10orf76
enteroviruses
lipid transfer
Membrane trafficking
Molecular modelling
Organelles
phosphatidylinositol
phosphatidylinositol 4‐kinase
Phosphatidylinositols
Phosphoinositides
PI4K
PI4KA
PI4KB
picornaviruses
Protein Binding
Reactive Oxygen Species
Replication
RNA viruses
Viral infections
Virus Replication - physiology
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Summary:Lipid phosphoinositides are master signaling molecules in eukaryotic cells and key markers of organelle identity. Because of these important roles, the kinases and phosphatases that generate phosphoinositides must be tightly regulated. Viruses can manipulate this regulation, with the Type III phosphatidylinositol 4‐kinases (PI4KA and PI4KB) being hijacked by many RNA viruses to mediate their intracellular replication through the formation of phosphatidylinositol 4‐phosphate (PI4P)‐enriched replication organelles (ROs). Different viruses have evolved unique approaches toward activating PI4K enzymes to form ROs, through both direct binding of PI4Ks and modulation of PI4K accessory proteins. This review will focus on PI4KA and PI4KB and discuss their roles in signaling, functions in membrane trafficking and manipulation by viruses. Our focus will be the molecular basis for how PI4KA and PI4KB are activated by both protein‐binding partners and post‐translational modifications, with an emphasis on understanding the different molecular mechanisms viruses have evolved to usurp PI4Ks. We will also discuss the chemical tools available to study the role of PI4Ks in viral infection. The phosphatidylinositol 4‐kinases (PI4Ks) are critical regulators of membrane trafficking and phosphoinositide metabolism at the Golgi and Plasma Membrane. Viruses can manipulate PI4K signalling, with PI4KA and PI4KB being hijacked by many RNA viruses to mediate their intracellular replication through the formation of phosphatidylinositol 4‐phosphate (PI4P) enriched replication organelles. PI4P generated at these organelles modulates the lipid composition to generate an environment conducive to viral replication
ISSN:1398-9219
1600-0854
DOI:10.1111/tra.12841