TY - JOUR TI - Building plus strand viral RNA replication platforms DO - https://doi.org/doi:10.7282/T3B27S8N PY - 2013 AB - Many RNA viruses remodel intracellular membranes of their hosts to generate specialized sites for RNA replication. How membranes are remodeled and what properties make them conducive for replication are unknown. Here we show how RNA viruses can manipulate multiple components of the cellular secretory pathway to generate organelles specialized for replication that are distinct in protein and lipid composition from the host cell. Specific viral proteins modulate effector recruitment by Arf1 GTPase and its guanine nucleotide exchange factor GBF1, promoting preferential recruitment of phosphatidylinositol-4-kinase IIIβ (PI4KIIIβ) to membranes over coat proteins, yielding uncoated phosphatidylinositol-4-phosphate (PI4P) lipid-enriched organelles. The PI4P-rich lipid microenvironment is essential for both enteroviral and flaviviral RNA replication; PI4KIIIβ inhibition interferes with this process. The potential mechanism by which PI4P mediated viral RNA replication are either tethering RdRP protein to replication membranes or regulating the RdRP and its precursor protein enzymatic activity. Our findings reveal how RNA viruses can selectively exploit specific elements of the host to form specialized organelles where cellular phosphoinositide lipids are key to regulating viral RNA replication. KW - Biology KW - Phosphoinositides KW - RNA viruses KW - RNA--Synthesis KW - Viruses--Reproduction LA - eng ER -