Inhibition of hepatitis C virus replication by chloroquine targeting virus-associated autophagy

Abstract

The results of this study suggest that the replication of HCV replicon utilizes machinery involving cellular autophagic proteolysis. The therapy targeted to autophagic proteolysis by using chloroquine may provide a new therapeutic option against chronic hepatitis C.

Replication of Hepatitis C Virus RNA on Autophagosomal Membranes

“…Recent studies indicated that HCV perturbs the autophagic pathway to induce the accumulation of autophagosomes in hepatoma cells (2)(3)(4)(5)(6)(7)(8)(9). Autophagy plays an important role in the removal of damaged organelles and protein aggregates from cells for recycling and is important for maintaining cellular homeostasis.…”

“…16). HCV has also been shown to perturb the autophagic pathway to cause the accumulation of autophagosomes (2)(3)(4)(5)(6)(7)(8). This perturbation is mediated by the unfolded protein response, which is activated by endoplasmic reticulum stress (3,4).…”

“…However, there are controversies regarding how the autophagic pathway may assist HCV replication, as some studies suggested that it enhanced HCV RNA replication, whereas others suggested that it might affect the release of HCV particles or the translation of the HCV RNA (3,(5)(6)(7)17). These controversies may be caused by a variety of reasons, including the use of different experimental systems such as transfection using the HCV genomic RNA or infection using the HCV particles, and the selection of different autophagic cellular factors for the RNAi knockdown experiments.…”

Changes in Autophagic Response in Patients with Chronic Hepatitis C Virus Infection

“…[5][6][7][8][9][10][11] In vitro, HCV induced autophagosome formation but was not able to enhance autophagic protein degradation suggesting an inefficient fusion between autophagosomes and lysosomes. 2,6 The results of ultrastructural morphometry obtained in the present study could indirectly support this view.…”

“…4 Several recent in vitro studies have suggested that the autophagic pathway is involved in HCV replication in cultured cells. [5][6][7][8][9][10][11] However, the relevance of such findings in vivo remains unknown because autophagy has never been assessed in chronic hepatitis C (CHC) patients. 2,4 The aims of the present study were to evaluate the autophagic response in CHC patients, and to identify factors influencing the autophagy level in such patients.…”