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

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 ge...

Full description

Saved in:
Bibliographic Details
Published in:Cell 2010-05, Vol.141 (5), p.799-811
Main Authors: Hsu, Nai-Yun, Ilnytska, Olha, Belov, Georgiy, Santiana, Marianita, Chen, Ying-Han, Takvorian, Peter M., Pau, Cyrilla, van der Schaar, Hilde, Kaushik-Basu, Neerja, Balla, Tamas, Cameron, Craig E., Ehrenfeld, Ellie, van Kuppeveld, Frank J.M., Altan-Bonnet, Nihal
Format: Article
Language:English
Subjects:
CELLBIO
Coat protein
Endoplasmic Reticulum - metabolism
Enterovirus
Enterovirus - metabolism
Flavivirus - metabolism
HeLa Cells
Humans
MICROBIO
Phosphatidylinositol Phosphates - metabolism
RNA, Viral - metabolism
Secretory Pathway
Virus Replication
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 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; 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. [Display omitted] [Display omitted] ► RNA viruses generate specialized RNA replication organelles enriched in PI4P lipids ► Host PI4KIIIβ enzyme is co-opted by the virus to generate PI4P lipid-rich organelles ► Enteroviral RNA polymerases specifically and preferentially bind PI4P lipids ► PI4P microenvironment is essential for enteroviral and flaviviral RNA synthesis
ISSN:0092-8674
1097-4172
DOI:10.1016/j.cell.2010.03.050