title: Host apolipoprotein B messenger RNA-editing enzyme catalytic polypeptide-like 3G is an innate defensive factor and drug target against hepatitis C virus.
abstract: Host cellular factor apolipoprotein B messenger RNA (mRNA)-editing enzyme catalytic polypeptide-like 3G (hA3G) is a cytidine deaminase that inhibits a group of viruses including human immunodeficiency virus-1 (HIV-1). In the continuation of our research on hA3G, we found that hA3G stabilizing compounds significantly inhibited hepatitis C virus (HCV) replication. Therefore, this study investigated the role of hA3G in HCV replication. Introduction of external hA3G into HCV-infected Huh7.5 human hepatocytes inhibited HCV replication; knockdown of endogenous hA3G enhanced HCV replication. Exogenous HIV-1 virion infectivity factor (Vif) decreased intracellular hA3G and therefore enhanced HCV proliferation, suggesting that the presence of Vif might be an explanation for the HIV-1/HCV coinfection often observed in HIV-1(+) individuals. Treatment of the HCV-infected Huh7.5 cells with RN-5 or IMB-26, two known hA3G stabilizing compounds, increased intracellular hA3G and accordingly inhibited HCV replication. The compounds inhibit HCV through increasing the level of hA3G incorporated into HCV particles, but not through inhibiting HCV enzymes. However, G/A hypermutation in the HCV genome were not detected, suggesting a new antiviral mechanism of hA3G in HCV, different from that in HIV-1. Stabilization of hA3G by RN-5 was safe in vivo.
  
  
  CONCLUSIONS
  hA3G appears to be a cellular restrict factor against HCV and could be a potential target for drug discovery.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Zong-Gen
authors.initials: ZG
authors.lastname: Peng
authors.forename: Zhi-Yun
authors.initials: ZY
authors.lastname: Zhao
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Li
authors.forename: Yu-Ping
authors.initials: YP
authors.lastname: Wang
authors.forename: Lan-Hu
authors.initials: LH
authors.lastname: Hao
authors.forename: Bo
authors.initials: B
authors.lastname: Fan
authors.forename: Yu-Huan
authors.initials: YH
authors.lastname: Li
authors.forename: Yue-Ming
authors.initials: YM
authors.lastname: Wang
authors.forename: Yong-Qiang
authors.initials: YQ
authors.lastname: Shan
authors.forename: Yan-Xing
authors.initials: YX
authors.lastname: Han
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Zhu
authors.forename: Jian-Rui
authors.initials: JR
authors.lastname: Li
authors.forename: Xue-Fu
authors.initials: XF
authors.lastname: You
authors.forename: Zhuo-Rong
authors.initials: ZR
authors.lastname: Li
authors.forename: Jian-Dong
authors.initials: JD
authors.lastname: Jiang
mesh_terms: D000071479:APOBEC-1 Deaminase; D000818:Animals; D000840:Anisoles / Q000494:pharmacology*; D001549:Benzamides / Q000494:pharmacology*; D002460:Cell Line; D003564:Cytidine Deaminase / Q000378:metabolism* / Q000627:therapeutic use; D016174:Hepacivirus / Q000187:drug effects*; D006526:Hepatitis C / Q000188:drug therapy; D006801:Humans; D007113:Immunity, Innate; D051379:Mice; D017393:RNA Editing / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects
chemical_list: C558672:(3-(alpha-bromopropyl)amino-4-methoxybenzene) formyl (3',4',5'-trimethoxybenzene) amide; D000840:Anisoles; D001549:Benzamides; D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; C000605090:Apobec1 protein, mouse; D003564:Cytidine Deaminase