Viral Reorganization of the Secretory Pathway Generates Distinct Organelles for RNA Replication

Overview

Journal Cell

Publisher Cell Press

Specialty Cell Biology

Date 2010 Jun 1

PMID 20510927

Citations 424

Authors

Nai-Yun Hsu

Olha Ilnytska

Georgiy Belov

Marianita Santiana

Ying-Han Chen

Peter M Takvorian

Cyrilla Pau

Hilde van der Schaar

Neerja Kaushik-Basu

Tamas Balla

Craig E Cameron

Ellie Ehrenfeld

Frank J M van Kuppeveld

Nihal Altan-Bonnet

Affiliations

Soon will be listed here.

Abstract

Many RNA viruses remodel intracellular membranes 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 IIIbeta (PI4KIIIbeta) 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; PI4KIIIbeta inhibition interferes with this process; and enteroviral RNA polymerases specifically bind PI4P. These 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.

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