title: Suppression of autophagy by mycophenolic acid contributes to inhibition of HCV replication in human hepatoma cells.
abstract: Previous studies have shown that mycophenolic acid (MPA) has an anti-HCV activity. However, the mechanism of MPA-mediated inhibition of HCV replication remains to be determined. This study investigated whether MPA has an effect on autophagy, a cellular machinery required for HCV replication, thereby, inhibits HCV replication in Huh7 cells. MPA treatment of Huh7 cells could suppress autophagy, evidenced by decreased LC3B-II level and conversion of LC3B-I to LC3B-II, decreased autophagosome formation, and increased p62 level compared to MPA-untreated cells. Tunicamycin treatment or HCV infection could induce cellular autophagy, however, MPA also exhibited its inhibitory effect on tunicamycin- or HCV infection-induced autophagy. The expression of three autophagy-related genes, Atg3, Atg5, and Atg7 were identified to be inhibited by MPA treatment. Over-expression of these genes could partly recover HCV replication inhibited by MPA; however, silencing their expression by siRNAs could enhance the inhibitory effect of MPA on HCV. Collectively, these results reveal that suppression of autophagy by MPA plays a role in its anti-HCV activity. Down-regulating the expression of three autophagy-related genes by MPA involves in its antiviral mechanism.
authors.affiliation: Guangxi Key Laboratory of AIDS Prevention and Treatment &Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, China.|Guangxi Collaborative Innovation Center for Biomedicine, Life Sciences Institute, Guangxi Medical University, Nanning 530021, Guangxi, China.
authors.forename: Shoucai
authors.initials: S
authors.lastname: Fang
authors.affiliation: Guangxi Key Laboratory of AIDS Prevention and Treatment &Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, China.|Division of HIV/AIDS Control and Prevention, Guangxi Center for Disease Control and Prevention, Nanning 530021, Guangxi, China.
authors.forename: Jinming
authors.initials: J
authors.lastname: Su
authors.affiliation: Guangxi Key Laboratory of AIDS Prevention and Treatment &Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, China.|Guangxi Collaborative Innovation Center for Biomedicine, Life Sciences Institute, Guangxi Medical University, Nanning 530021, Guangxi, China.
authors.forename: Bingyu
authors.initials: B
authors.lastname: Liang
authors.affiliation: Guangxi Key Laboratory of AIDS Prevention and Treatment &Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, China.|Guangxi Collaborative Innovation Center for Biomedicine, Life Sciences Institute, Guangxi Medical University, Nanning 530021, Guangxi, China.
authors.forename: Xu
authors.initials: X
authors.lastname: Li
authors.affiliation: Guangxi Key Laboratory of AIDS Prevention and Treatment &Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Li
authors.affiliation: Guangxi Key Laboratory of AIDS Prevention and Treatment &Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, China.|Guangxi Collaborative Innovation Center for Biomedicine, Life Sciences Institute, Guangxi Medical University, Nanning 530021, Guangxi, China.
authors.forename: Junjun
authors.initials: J
authors.lastname: Jiang
authors.affiliation: Guangxi Key Laboratory of AIDS Prevention and Treatment &Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, China.|Guangxi Collaborative Innovation Center for Biomedicine, Life Sciences Institute, Guangxi Medical University, Nanning 530021, Guangxi, China.
authors.forename: Jiegang
authors.initials: J
authors.lastname: Huang
authors.affiliation: Guangxi Key Laboratory of AIDS Prevention and Treatment &Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, China.|Guangxi Collaborative Innovation Center for Biomedicine, Life Sciences Institute, Guangxi Medical University, Nanning 530021, Guangxi, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Guangxi Key Laboratory of AIDS Prevention and Treatment &Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, China.|Guangxi Collaborative Innovation Center for Biomedicine, Life Sciences Institute, Guangxi Medical University, Nanning 530021, Guangxi, China.
authors.forename: Chuanyi
authors.initials: C
authors.lastname: Ning
authors.affiliation: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Jieliang
authors.initials: J
authors.lastname: Li
authors.affiliation: Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA 19140, USA.
authors.forename: Wenzhe
authors.initials: W
authors.lastname: Ho
authors.affiliation: Institute of Human Virology and Key Laboratory of Tropical Disease Control of Ministry of Education, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Li
authors.affiliation: Geriatrics Digestion Department of Internal Medicine, The First Affiliated Hospital of Guangxi Medical University, Nanning 530021, Guangxi, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Guangxi Key Laboratory of AIDS Prevention and Treatment &Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, China.|Guangxi Collaborative Innovation Center for Biomedicine, Life Sciences Institute, Guangxi Medical University, Nanning 530021, Guangxi, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Liang
authors.affiliation: Guangxi Key Laboratory of AIDS Prevention and Treatment &Guangxi Universities Key Laboratory of Prevention and Control of Highly Prevalent Disease, School of Public Health, Guangxi Medical University, Nanning 530021, Guangxi, China.|Guangxi Collaborative Innovation Center for Biomedicine, Life Sciences Institute, Guangxi Medical University, Nanning 530021, Guangxi, China.
authors.forename: Li
authors.initials: L
authors.lastname: Ye
mesh_terms: D001343:Autophagy / Q000187:drug effects*; D006528:Carcinoma, Hepatocellular / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D045744:Cell Line, Tumor; D016174:Hepacivirus / Q000502:physiology*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D009173:Mycophenolic Acid / Q000494:pharmacology*; D009363:Neoplasm Proteins / Q000378:metabolism*; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D009363:Neoplasm Proteins; D009173:Mycophenolic Acid