The SIRT1 inhibitor, nicotinamide, inhibits hepatitis B virus replication in vitro and in vivo

The SIRT1 inhibitor, nicotinamide, inhibits hepatitis B virus replication in vitro and in vivo We previously reported that SIRT1, an NAD + -dependent deacetylase belonging to the class III histone deacetylases, enhances hepatitis virus B (HBV) replication by targeting the transcription factor AP-1. However, the potential antiviral effects of nicotinamide, a SIRT1 inhibitor, have not yet been explored. In this study, we show that nicotinamide exhibits potent anti-HBV activity with little cytotoxicity. Nicotinamide suppressed both HBV DNA replicative intermediates and 3.5-kb mRNA expression. Moreover, nicotinamide treatment also suppressed core protein expression and the secretion of the hepatitis B surface antigen (HBsAg) and the hepatitis B e antigen (HBeAg) in HBV-expressing cell models. Importantly, nicotinamide treatment suppressed serum HBV DNA, HBsAg and HBeAg levels and liver HBV DNA in HBV-transgenic mice. Furthermore, using a dual-luciferase reporter assay, it was found that nicotinamide exhibited a marked inhibitory effect on the HBV core, SpI, SpII and X promoters, accompanied by decreased expression of the transcription factors AP-1, C/EBPα and PPARα. Therefore, nicotinamide suppresses HBV replication in vitro and in vivo by diminishing HBV promoter activity. This study highlights the potential application of nicotinamide in HBV therapy. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Virology Springer Journals

The SIRT1 inhibitor, nicotinamide, inhibits hepatitis B virus replication in vitro and in vivo

Loading next page...
 
/lp/springer_journal/the-sirt1-inhibitor-nicotinamide-inhibits-hepatitis-b-virus-STKlqMtFRg
Publisher
Springer Journals
Copyright
Copyright © 2016 by Springer-Verlag Wien
Subject
Biomedicine; Virology; Medical Microbiology; Infectious Diseases
ISSN
0304-8608
eISSN
1432-8798
D.O.I.
10.1007/s00705-015-2712-8
Publisher site
See Article on Publisher Site

Abstract

We previously reported that SIRT1, an NAD + -dependent deacetylase belonging to the class III histone deacetylases, enhances hepatitis virus B (HBV) replication by targeting the transcription factor AP-1. However, the potential antiviral effects of nicotinamide, a SIRT1 inhibitor, have not yet been explored. In this study, we show that nicotinamide exhibits potent anti-HBV activity with little cytotoxicity. Nicotinamide suppressed both HBV DNA replicative intermediates and 3.5-kb mRNA expression. Moreover, nicotinamide treatment also suppressed core protein expression and the secretion of the hepatitis B surface antigen (HBsAg) and the hepatitis B e antigen (HBeAg) in HBV-expressing cell models. Importantly, nicotinamide treatment suppressed serum HBV DNA, HBsAg and HBeAg levels and liver HBV DNA in HBV-transgenic mice. Furthermore, using a dual-luciferase reporter assay, it was found that nicotinamide exhibited a marked inhibitory effect on the HBV core, SpI, SpII and X promoters, accompanied by decreased expression of the transcription factors AP-1, C/EBPα and PPARα. Therefore, nicotinamide suppresses HBV replication in vitro and in vivo by diminishing HBV promoter activity. This study highlights the potential application of nicotinamide in HBV therapy.

Journal

Archives of VirologySpringer Journals

Published: Mar 1, 2016

References

  • Use of Niacin as a Drug
    DiPalma, JR; Thayer, WS
  • Nicotinamide reduces acute cortical neuronal death and edema in the traumatically injured brain
    Hoane, MR; Gilbert, DR; Holland, MA; Pierce, JL
  • Hepatitis B virus X protein: a multifunctional viral regulator
    Murakami, S
  • Nicotinamide inhibits HIV-1 in both acute and chronic in vitro infection
    Murray, MF; Srinivasan, A
  • Control of hepatitis B virus at the level of transcription
    Quasdorff, M; Protzer, U
  • SIRT2 regulates ciliogenesis and contributes to abnormal centrosome amplification caused by loss of polycystin-1
    Zhou, X; Fan, LX; Li, K; Ramchandran, R; Calvet, JP; Li, X

You’re reading a free preview. Subscribe to read the entire article.


DeepDyve is your
personal research library

It’s your single place to instantly
discover and read the research
that matters to you.

Enjoy affordable access to
over 18 million articles from more than
15,000 peer-reviewed journals.

All for just $49/month

Explore the DeepDyve Library

Search

Query the DeepDyve database, plus search all of PubMed and Google Scholar seamlessly

Organize

Save any article or search result from DeepDyve, PubMed, and Google Scholar... all in one place.

Access

Get unlimited, online access to over 18 million full-text articles from more than 15,000 scientific journals.

Your journals are on DeepDyve

Read from thousands of the leading scholarly journals from SpringerNature, Elsevier, Wiley-Blackwell, Oxford University Press and more.

All the latest content is available, no embargo periods.

See the journals in your area

DeepDyve

Freelancer

DeepDyve

Pro

Price

FREE

$49/month
$360/year

Save searches from
Google Scholar,
PubMed

Create lists to
organize your research

Export lists, citations

Read DeepDyve articles

Abstract access only

Unlimited access to over
18 million full-text articles

Print

20 pages / month

PDF Discount

20% off