Viral reorganization of the secretory pathway generates distinct organelles for RNA replication

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

doi:10.1016/j.cell.2010.03.050

Viral reorganization of the secretory pathway generates distinct organelles for RNA replication

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

Research output: Contribution to journal › Article › Academic › peer-review

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.

Original language	English
Pages (from-to)	799-811
Number of pages	13
Journal	Cell
Volume	141
Issue number	5
DOIs	https://doi.org/10.1016/j.cell.2010.03.050
Publication status	Published - 2010

Keywords

Endoplasmic Reticulum
Enterovirus
Flavivirus
HeLa Cells
Humans
Phosphatidylinositol Phosphates
RNA, Viral
Secretory Pathway
Virus Replication

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10.1016/j.cell.2010.03.050

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Hsu, N.-Y., Ilnytska, O., Belov, G., Santiana, M., Chen, Y.-H., Takvorian, P. M., Pau, C., van der Schaar, H., Kaushik-Basu, N., Balla, T., Cameron, C. E., Ehrenfeld, E., van Kuppeveld, F. J. M., & Altan-Bonnet, N. (2010). Viral reorganization of the secretory pathway generates distinct organelles for RNA replication. Cell, 141(5), 799-811. https://doi.org/10.1016/j.cell.2010.03.050

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title = "Viral reorganization of the secretory pathway generates distinct organelles for RNA replication",

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.",

keywords = "Endoplasmic Reticulum, Enterovirus, Flavivirus, HeLa Cells, Humans, Phosphatidylinositol Phosphates, RNA, Viral, Secretory Pathway, Virus Replication",

author = "Nai-Yun Hsu and Olha Ilnytska and Georgiy Belov and Marianita Santiana and Ying-Han Chen and Takvorian, {Peter M} and Cyrilla Pau and {van der Schaar}, Hilde and Neerja Kaushik-Basu and Tamas Balla and Cameron, {Craig E} and Ellie Ehrenfeld and {van Kuppeveld}, {Frank J M} and Nihal Altan-Bonnet",

year = "2010",

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language = "English",

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pages = "799--811",

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Hsu, N-Y, Ilnytska, O, Belov, G, Santiana, M, Chen, Y-H, Takvorian, PM, Pau, C, van der Schaar, H, Kaushik-Basu, N, Balla, T, Cameron, CE, Ehrenfeld, E, van Kuppeveld, FJM & Altan-Bonnet, N 2010, 'Viral reorganization of the secretory pathway generates distinct organelles for RNA replication', Cell, vol. 141, no. 5, pp. 799-811. https://doi.org/10.1016/j.cell.2010.03.050

TY - JOUR

T1 - Viral reorganization of the secretory pathway generates distinct organelles for RNA replication

AU - Hsu, Nai-Yun

AU - Ilnytska, Olha

AU - Belov, Georgiy

AU - Santiana, Marianita

AU - Chen, Ying-Han

AU - Takvorian, Peter M

AU - Pau, Cyrilla

AU - van der Schaar, Hilde

AU - Kaushik-Basu, Neerja

AU - Balla, Tamas

AU - Cameron, Craig E

AU - Ehrenfeld, Ellie

AU - van Kuppeveld, Frank J M

AU - Altan-Bonnet, Nihal

PY - 2010

Y1 - 2010

N2 - 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.

AB - 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.

KW - Endoplasmic Reticulum

KW - Enterovirus

KW - Flavivirus

KW - HeLa Cells

KW - Humans

KW - Phosphatidylinositol Phosphates

KW - RNA, Viral

KW - Secretory Pathway

KW - Virus Replication

U2 - 10.1016/j.cell.2010.03.050

DO - 10.1016/j.cell.2010.03.050

M3 - Article

C2 - 20510927

SN - 0092-8674

VL - 141

SP - 799

EP - 811

JO - Cell

JF - Cell

IS - 5

ER -

Viral reorganization of the secretory pathway generates distinct organelles for RNA replication

Abstract

Keywords

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