title: Inhibition of HBV replication by theophylline.
abstract: We have suggested recently that ATM-Rad3-Related (ATR) DNA damage signaling pathway, which responds to single-strand breaks in DNA, was activated in response to HBV infection. ATR knockdown cells showed decreased HBV DNA yields, implying HBV infection and replication activate and exploit the activated DNA damage response. Host cell proteins may constitute an attractive target for anti-HBV-1 therapeutics, since development of drug resistance against compounds targeting these cellular cofactor proteins is unlikely. In this study, we show that one of the clinically used compounds of ATR and ataxia telangiectasia-mutated (ATM) kinases inhibitor, theophylline (Tp), significantly reduced the yield of HBV DNA, HBsAg and HBeAg in HepG2215 cell culture system, furthermore, Tp could also suppress serum HBV DNA and HBsAg levels in the HBV-transgenic mice. Consistent with this result, immunohistology also showed reduced intensity of HBsAg staining on livers from Tp-treatment group. Taken together, these data indicated the feasibility of therapeutic approaches that target host cell proteins by inhibiting a cellular gene that was required for HBV replication and provided a potential approach for the prevention and treatment of HBV infection.
authors.affiliation: State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Biotechnology, Room 841, East District Building, No. 27 Taiping Road, Haidian District, Beijing 100850, China.
authors.forename: Zirui
authors.initials: Z
authors.lastname: Zheng
authors.forename: Junyan
authors.initials: J
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Sun
authors.forename: Ting
authors.initials: T
authors.lastname: Song
authors.forename: Congwen
authors.initials: C
authors.lastname: Wei
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Zhang
authors.forename: Guirong
authors.initials: G
authors.lastname: Rao
authors.forename: Guangming
authors.initials: G
authors.lastname: Chen
authors.forename: DeChao
authors.initials: D
authors.lastname: Li
authors.forename: Gongming
authors.initials: G
authors.lastname: Yang
authors.forename: Bao
authors.initials: B
authors.lastname: Han
authors.forename: Shi
authors.initials: S
authors.lastname: Wei
authors.forename: Cheng
authors.initials: C
authors.lastname: Cao
authors.forename: Hui
authors.initials: H
authors.lastname: Zhong
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002460:Cell Line; D004279:DNA, Viral / Q000097:blood; D004195:Disease Models, Animal; D006509:Hepatitis B / Q000188:drug therapy*; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000187:drug effects*; D022781:Hepatocytes / Q000821:virology; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008822:Mice, Transgenic; D013806:Theophylline / Q000494:pharmacology* / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D013806:Theophylline