Cell Biology

Exploiting an Exploiter

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Science  02 Jul 2010:
Vol. 329, Issue 5987, pp. 14
DOI: 10.1126/science.329.5987.14-c

Viruses have evolved diverse mechanisms to take control of the host cells in which they replicate. All plus-stranded RNA viruses, such as hepatitis A and poliovirus, use host cell membranes for replication in the cytoplasm. Coronaviruses such as SARS and mouse hepatitis virus (MHV), which infect the mammalian gastrointestinal and respiratory tracts, induce the formation of double membrane vesicles; the cellular origin of these membranes has been unclear. Reggiori et al. find that MHV accumulates cellular membranes by hijacking part of a protein degradation pathway known as ERAD, which is associated with the endoplasmic reticulum. As a quality-control step in protein degradation, the chaperone protein EDEM1 is sequestered in small vesicles away from the endoplasmic reticulum to distinct cellular compartments. MHV exploits this event to obtain endoplasmic reticulum–derived membranes for its own use. Both EDEM1 and the autophagy-associated protein LC3 associated with virus-induced double membrane vesicles, and down-regulation of LC3 protected cells from MHV infection. By identifying the mechanism whereby this coronavirus recruits host membranes for replication, the authors have identified potential therapeutic targets, which may also be applicable to other viruses in this family.

Cell Host Microbe 7, 500 (2010).

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