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World J Virol. May 12, 2013; 2(2): 32-48
Published online May 12, 2013. doi: 10.5501/wjv.v2.i2.32
Architecture and biogenesis of plus-strand RNA virus replication factories
David Paul, Ralf Bartenschlager
David Paul, Ralf Bartenschlager, Department of Infectious Diseases, Molecular Virology, University of Heidelberg, 69120 Heidelberg, Germany
Author contributions: Paul D and Bartenschlager R contributed equally to write this paper.
Supported by The DFG, SFB638, TP A5 and SFB/TRR83, TP 13
Correspondence to: Dr. Ralf Bartenschlager, Professor, Department of Infectious Diseases, Molecular Virology, University of Heidelberg, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany.
Telephone: +49-6221-564225 Fax: +49-6221-564570
Received: December 5, 2012
Revised: January 18, 2013
Accepted: January 23, 2013
Published online: May 12, 2013

Plus-strand RNA virus replication occurs in tight association with cytoplasmic host cell membranes. Both, viral and cellular factors cooperatively generate distinct organelle-like structures, designated viral replication factories. This compartmentalization allows coordination of the different steps of the viral replication cycle, highly efficient genome replication and protection of the viral RNA from cellular defense mechanisms. Electron tomography studies conducted during the last couple of years revealed the three dimensional structure of numerous plus-strand RNA virus replication compartments and highlight morphological analogies between different virus families. Based on the morphology of virus-induced membrane rearrangements, we propose two separate subclasses: the invaginated vesicle/spherule type and the double membrane vesicle type. This review discusses common themes and distinct differences in the architecture of plus-strand RNA virus-induced membrane alterations and summarizes recent progress that has been made in understanding the complex interplay between viral and co-opted cellular factors in biogenesis and maintenance of plus-strand RNA virus replication factories.

Keywords: Viral replication factory, Viral replication complex, Plus-strand RNA virus, Membrane remodeling, Virus-host interaction, Alphavirus, Enterovirus, Coronavirus, Flavivirus, Hepatitis C virus