Viral Reorganization of the Secretory Pathway Generates Distinct Organelles for RNA Replication
By Nai‐Yun Hsu, O. Ilnytska, G. Belov, M. Santiana, Ying-Han Chen, P. Takvorian, Cyrilla Pau, H. M. van der Schaar, Neerja Kaushik-Basu, T. Balla and 4 more. Cell, 2010
693 citations recorded by the source corpus.
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 micro-environment 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.
Subfields: Cardiology and Cardiovascular Medicine, Hepatology, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/10434eb42e10dd99eca095477cf20c0b5d1e0faf
How researchers see this paper
The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.
In Hepatology
In Molecular Biology
Citations in the corpus
- Dengue virus induced autophagy regulates lipid metabolism (2010, background): “In addition to alterations in lipid metabolism, HCV and some enteroviruses also depend on phospholipid signaling for replication (Berger et al., 2009; Berger and Randall, 2009; Borawski et al., 2009; Hsu et al., 2010; Li et al., 2009; Tai et al., 2009; Trotard et al., 2009; Vaillancourt et al., 2009”
- Fat(al) attraction: Picornaviruses Usurp Lipid Transfer at Membrane Contact Sites to Create Replication Organelles (2016, background): “The observation that replication is hampered when PI4P transported to the ER is not hydrolyzed upon knockdown of Sac1 [23,60] underscores the importance of the cholesterol/PI4P-counterflux for enterovirus replication.”
- Phosphoinositides: tiny lipids with giant impact on cell regulation. (2013, background): “Intriguingly, some HCV strains also require this enzyme for replication and inhibitors of PI4KB potently slow down viral replication (656).”
- Arf Family G Proteins and their regulators: roles in membrane transport, development and disease (2011, background): “PtdIns4Ks are essential for viral replication, and notably produce the PtdIns4P-enriched membrane environment that recruits the enteroviral RNA polymerase”