Inhibition of hepatitis B virus replication by a dNTPase-dependent function of the host restriction factor SAMHD1

Gi Uk Jeong; Il Hyun Park; Kwangseog Ahn; Byung Yoon Ahn

doi:10.1016/j.virol.2016.05.001

Inhibition of hepatitis B virus replication by a dNTPase-dependent function of the host restriction factor SAMHD1

Gi Uk Jeong, Il Hyun Park, Kwangseog Ahn, Byung Yoon Ahn

Department of Life Sciences

Research output: Contribution to journal › Article › peer-review

30 Citations (Scopus)

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.

Original language	English
Pages (from-to)	71-78
Number of pages	8
Journal	Virology
Volume	495
DOIs	https://doi.org/10.1016/j.virol.2016.05.001
Publication status	Published - 2016 Aug 1

Keywords

CccDNA
DNTPase
HBV restriction
SAMHD1

ASJC Scopus subject areas

Virology

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.virol.2016.05.001

Cite this

@article{3ac7470246d74c9fbc1fee47726d67b0,

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.",

keywords = "CccDNA, DNTPase, HBV restriction, SAMHD1",

author = "Jeong, {Gi Uk} and Park, {Il Hyun} and Kwangseog Ahn and Ahn, {Byung Yoon}",

note = "Funding Information: We are grateful to Wenhui Li and Wang-Shick Ryu for NTCP and pHBV1.2. This work was supported by the Basic Science Research Program of the National Research Foundation and the Ministry of Education of the Republic of Korea ( #2015R1D1A1A09057096 ). The preliminary study was supported by Korea University, the Republic of Korea . G. U. Jeong and I. H. Park were supported by the BK21 Plus program of the Ministry of Education of the Republic of Korea. Publisher Copyright: {\textcopyright} 2016 Elsevier Inc.",

year = "2016",

month = aug,

day = "1",

doi = "10.1016/j.virol.2016.05.001",

language = "English",

volume = "495",

pages = "71--78",

journal = "Virology",

issn = "0042-6822",

publisher = "Academic Press Inc.",

}

TY - JOUR

T1 - Inhibition of hepatitis B virus replication by a dNTPase-dependent function of the host restriction factor SAMHD1

AU - Jeong, Gi Uk

AU - Park, Il Hyun

AU - Ahn, Kwangseog

AU - Ahn, Byung Yoon

N1 - Funding Information: We are grateful to Wenhui Li and Wang-Shick Ryu for NTCP and pHBV1.2. This work was supported by the Basic Science Research Program of the National Research Foundation and the Ministry of Education of the Republic of Korea ( #2015R1D1A1A09057096 ). The preliminary study was supported by Korea University, the Republic of Korea . G. U. Jeong and I. H. Park were supported by the BK21 Plus program of the Ministry of Education of the Republic of Korea. Publisher Copyright: © 2016 Elsevier Inc.

PY - 2016/8/1

Y1 - 2016/8/1

N2 - 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.

AB - 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.

KW - CccDNA

KW - DNTPase

KW - HBV restriction

KW - SAMHD1

UR - http://www.scopus.com/inward/record.url?scp=84966429498&partnerID=8YFLogxK

U2 - 10.1016/j.virol.2016.05.001

DO - 10.1016/j.virol.2016.05.001

M3 - Article

C2 - 27179347

AN - SCOPUS:84966429498

SN - 0042-6822

VL - 495

SP - 71

EP - 78

JO - Virology

JF - Virology

ER -

Inhibition of hepatitis B virus replication by a dNTPase-dependent function of the host restriction factor SAMHD1

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

Other files and links

Fingerprint

Cite this