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Review
. 2011 Sep;3(9):1610-23.
doi: 10.3390/v3091610. Epub 2011 Sep 5.

Unconventional use of LC3 by coronaviruses through the alleged subversion of the ERAD tuning pathway

Fulvio Reggiori  1 , Cornelis A M de Haan, Maurizio Molinari
Affiliations
Review

Unconventional use of LC3 by coronaviruses through the alleged subversion of the ERAD tuning pathway

Fulvio Reggiori et al. Viruses. 2011 Sep.

Abstract

Pathogens of bacterial and viral origin hijack pathways operating in eukaryotic cells in many ways in order to gain access into the host, to establish themselves and to eventually produce their progeny. The detailed molecular characterization of the subversion mechanisms devised by pathogens to infect host cells is crucial to generate targets for therapeutic intervention. Here we review recent data indicating that coronaviruses probably co-opt membranous carriers derived from the endoplasmic reticulum, which contain proteins that regulate disposal of misfolded polypeptides, for their replication. In addition, we also present models describing potential mechanisms that coronaviruses could employ for this hijacking.

Keywords: EDEM1; EDEMosomes; ER quality control; ERAD; MHV; OS-9; SARS-coronavirus; autophagy; coronaviruses; double-membrane vesicles; nidoviruses.

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Figures

Figure 1.
Figure 1.
Ultrastructure of membrane-associated replicative structures induced by mouse hepatitis virus (MHV) in host cells. Mouse LR7 cells inoculated with the MHV-A59 strain were fixed at 10 h post-infection and processed for conventional EM. Double membrane vesicles (DMVs) are often found clustered together in close proximity of a small network of membranes, the CMs, which are morphologically distinct but have identical viral protein composition. The asterisks mark the DMVs. CM, convoluted membranes; M, mitochondria; L, lysosome. Size bar, 500 nm.
Figure 2.
Figure 2.
ERAD tuning. Many ERAD regulators are short-lived proteins at steady state. EDEM1 and OS-9 are canonical ERAD tuning substrates. Their selective removal from the ER lumen can be subdivided in three steps. (1) Association with an elusive membrane receptor allows segregation of EDEM1, OS-9 and possibly other ERAD factors (EF) from conventional, long-lived ER-resident chaperones (in grey); (2) The ERAD regulators exit the ER in small, LC3-I-coated vesicles, the EDEMosomes; (3) EDEMosomes deliver their content to endo-lysosomal compartments for disposal.
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