title: Inhibition of hepatitis B virus replication by ligand-mediated activation of RNase L.
abstract: RNase L is a cellular endoribonuclease that is activated by 2',5'-linked oligoadenylates (2-5A), which are unique and specific ligands synthesized by a family of interferon-inducible, dsRNA-activated enzymes named oligoadenylate synthetases. In the typical antiviral pathway, activated RNase L degrades viral and cellular RNAs, thus limiting viral replication and spread. Although the antiviral activity of RNase L has been demonstrated for several RNA viruses, there is little evidence regarding its role against DNA viruses. In the present study, the potential antiviral activity of RNase L against hepatitis B virus (HBV) was explored utilizing the recently reported infection protocol based on human hepatoma HepG2 cells stably complemented with the virus entry factor NTCP. Viral replication and expression in this cell type was markedly inhibited by poly(I:C)- or 2-5A-mediated activation of RNase L; however, the inhibition was significantly reversed by RNase L knockdown. Further analysis in HBV1.2-transfected Huh-7 hepatoma cells indicated that the antiviral activity of RNase L depends on its ribonuclease function. We also provide evidence for the specific roles of OAS family members in this process. These results suggest that HBV replication can be regulated through interferon-mediated RNA decay pathways and that activation of these host antiviral factors may represent a novel therapeutic strategy for HBV infection.
authors: Department of Life Sciences, Korea University, Anam-dong 5-1, Seoul 136-701, Republic of Korea.
authors: Il-Hyun
authors: IH
authors: Park
authors: Department of Life Sciences, Korea University, Anam-dong 5-1, Seoul 136-701, Republic of Korea.
authors: Young-Chan
authors: YC
authors: Kwon
authors: Department of Biochemistry, Yonsei University, Yonsei-ro 50, Seoul 120-749, Republic of Korea.
authors: Wang-Shick
authors: WS
authors: Ryu
authors: Department of Life Sciences, Korea University, Anam-dong 5-1, Seoul 136-701, Republic of Korea. Electronic address: ahnbyung@korea.ac.kr.
authors: Byung-Yoon
authors: BY
authors: Ahn
mesh_terms: D000227:Adenine Nucleotides / Q000494:pharmacology; D002460:Cell Line; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism*; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D006515:Hepatitis B virus / Q000187:drug effects / Q000502:physiology*; D006801:Humans; D007527:Isoenzymes; D008024:Ligands; D009843:Oligoribonucleotides / Q000494:pharmacology; D011070:Poly I-C / Q000494:pharmacology; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000227:Adenine Nucleotides; D007527:Isoenzymes; D008024:Ligands; D009843:Oligoribonucleotides; C023505:2',5'-oligoadenylate; D004722:Endoribonucleases; C031956:2-5A-dependent ribonuclease; D011070:Poly I-C
keywords: Hepatitis B virus; Interferon; Oligoadenylate synthetase; RNA decay; RNase L