Mark Denison
Last active: 2/22/2016

Coronavirus replication complex formation utilizes components of cellular autophagy.

Prentice E, Jerome WG, Yoshimori T, Mizushima N, Denison MR
J Biol Chem. 2004 279 (11): 10136-41

PMID: 14699140 · DOI:10.1074/jbc.M306124200

The coronavirus mouse hepatitis virus (MHV) performs RNA replication on double membrane vesicles (DMVs) in the cytoplasm of the host cell. However, the mechanism by which these DMVs form has not been determined. Using genetic, biochemical, and cell imaging approaches, the role of autophagy in DMV formation and MHV replication was investigated. The results demonstrated that replication complexes co-localize with the autophagy proteins, microtubule-associated protein light-chain 3 and Apg12. MHV infection induces autophagy by a mechanism that is resistant to 3-methyladenine inhibition. MHV replication is impaired in autophagy knockout, APG5-/-, embryonic stem cell lines, but wild-type levels of MHV replication are restored by expression of Apg5 in the APG5-/-cells. In MHV-infected APG5-/-cells, DMVs were not detected; rather, the rough endoplasmic reticulum was dramatically swollen. The results of this study suggest that autophagy is required for formation of double membrane-bound MHV replication complexes and that DMV formation significantly enhances the efficiency of replication. Furthermore, the rough endoplasmic reticulum is implicated as the possible source of membranes for replication complexes.

MeSH Terms (22)

Adenine Animals Autophagy Autophagy-Related Protein 12 Blotting, Western Cell Division Cell Line Coronavirus Cytoplasm Embryo, Mammalian Endoplasmic Reticulum, Rough Mice Microscopy, Electron Microscopy, Fluorescence Microtubule-Associated Proteins Phylogeny Protein Binding Proteins Protein Transport Saccharomyces cerevisiae Proteins Stem Cells Time Factors

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