title: Inhibition of hepatitis B virus replication by a dNTPase-dependent function of the host restriction factor SAMHD1.
abstract: SAMHD1 is a cellular protein that possesses dNTPase activity and inhibits retroviruses and DNA viruses through the depletion of cellular dNTPs. However, recent evidence suggests the existence of alternative or additional mechanisms that involve novel nuclease activities. Hepatitis B virus is a DNA virus but resembles retroviruses in that its DNA genome is synthesized via reverse transcription of an RNA transcript. SAMHD1 was shown to inhibit the expression and replication of a transfected HBV DNA. We further investigated the antiviral mechanisms in a newly developed infection assay. Our data indicated that SAMHD1 exerts a profound antiviral effect. In addition, unlike previous findings, our results demonstrate the essential role of SAMHD1 dNTPase. SAMHD1 did not affect virion-derived cccDNA and gene expression but specifically inhibited viral DNA synthesis. These results indicate that SAMHD1 inhibits HBV replication at the reverse transcription step, most likely through the depletion of cellular dNTPs.
authors.affiliation: Department of Life Sciences, Korea University, Seoul, Republic of Korea.
authors.forename: Gi Uk
authors.initials: GU
authors.lastname: Jeong
authors.affiliation: Department of Life Sciences, Korea University, Seoul, Republic of Korea.
authors.forename: Il-Hyun
authors.initials: IH
authors.lastname: Park
authors.affiliation: Department of Biological Sciences, Seoul National University, Seoul, Republic of Korea.
authors.forename: Kwangseog
authors.initials: K
authors.lastname: Ahn
authors.affiliation: Department of Life Sciences, Korea University, Seoul, Republic of Korea. Electronic address: ahnbyung@korea.ac.kr.
authors.forename: Byung-Yoon
authors.initials: BY
authors.lastname: Ahn
mesh_terms: D002460:Cell Line; D004261:DNA Replication; D006509:Hepatitis B / Q000378:metabolism* / Q000821:virology*; D006515:Hepatitis B virus / Q000502:physiology*; D054884:Host-Pathogen Interactions; D006801:Humans; D020559:Monomeric GTP-Binding Proteins / Q000378:metabolism*; D048348:Reverse Transcription; D000076106:SAM Domain and HD Domain-Containing Protein 1; D014779:Virus Replication
chemical_list: D000076106:SAM Domain and HD Domain-Containing Protein 1; C484280:SAMHD1 protein, human; D020559:Monomeric GTP-Binding Proteins
keywords: HBV restriction; SAMHD1; cccDNA; dNTPase