Virology

Hitchhiking in Membrane Traffic

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Science  29 Aug 2008:
Vol. 321, Issue 5893, pp. 1135
DOI: 10.1126/science.321.5893.1135b

Autophagy is a process whereby cells rid themselves of defunct organelles and proteins by enclosing them in a double-membraned vesicle that then fuses with and is degraded by a lysosome. Autophagy is important in general cellular homeostasis, in development, and in certain aspects of pathology. In complementary papers, Sir et al. found that cells infected with the hepatitis C virus (HCV) accumulate autophagosomes but fail to increase autophagic degradation, probably because of a failure in autophagosome-lysosome fusion. The increase in morphologically distinguishable autophagosomes required the expression of genes known to be important in autophagy, but also required the activity of the unfolded protein response signaling pathway, which is a stress-response pathway involved in the recognition of aberrant proteins in the endoplasmic reticulum. Blocking HCV-dependent autophagosome accumulation by blocking autophagy or by blocking the unfolded protein response pathway suppressed virus replication. Thus, it seems that HCV exploits degradation-defective autophagosomes during its replication cycle. — SMH

Hepatology 48, 10.1002/hep.22464 (2008); Autophagy 4, 830 (2008).

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