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

Nihal Altan-Bonnet et al. 2010. cell 141, 799-811

Speaker: Pei- Huan Lee (李佩寰)                         Time: 13:00-14:00, May 25, 2011

Commentator: Yao Chang, Ph.D. (張堯老師)      Place: Room 601

Abstract

Viruses rely on a living host cell for reproduction. Some plus-strand RNA viruses can remodel host intracellular membrane to help their replication and assembly. However the properties of these required replication membrane are not unclear. In this study, the authors demonstrated that plus-strand RNA viruses can selectively recruit host factors to generate organelle with a lipid composition which suitable for viral replication. They found that cellular GBF1 , a guanine nucleotide exchange factor (GEF) of the small Ras-family GTPase Arf1, and Arf1 were colocalized with viral replication complex, and further recruited other cellular proteins and lipids to form atypical organelles at ER exit sites during Coxsackievirus B 3 infection. The enteroviral protein 3A could selectively enhance the recruitment of PI4K3b which is a critical kinase for PI4P lipid synthesis to help membrane remodeling. These newly synthesized PI4P lipids by Coxsackievirus B 3 3A directly bound the viral RNA polymerase and facilitated viral RNA synthesis. They demonstrated that the PIP4 lipid- enriched microenvironments are also required for flavivirus RNA replication. In conclusion, the authors show that plus-strand RNA viruses remodel host secretory pathway to make lipid-enriched organelles for viral replication .

References

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