Inhibition of hepatitis B viral entry by nucleic acid polymers in HepaRG cells and primary human hepatocytes.
Hepatitis B virus (HBV) infection remains a major public health concern worldwide with 240 million individuals chronically infected and at risk of developing cirrhosis and hepatocellular carcinoma. Current treatments rarely cure chronic hepatitis B infection, highlighting the need for new anti-HBV d...
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doaj-371cae425a9948e3882cd9b9811f058f2020-11-25T02:12:00ZengPublic Library of Science (PLoS)PLoS ONE1932-62032017-01-01126e017969710.1371/journal.pone.0179697Inhibition of hepatitis B viral entry by nucleic acid polymers in HepaRG cells and primary human hepatocytes.Clément GuillotNora MartelFrançoise BerbyIsabelle BordesOlivier HantzMatthieu BlanchetCamille SureauAndrew VaillantIsabelle CheminHepatitis B virus (HBV) infection remains a major public health concern worldwide with 240 million individuals chronically infected and at risk of developing cirrhosis and hepatocellular carcinoma. Current treatments rarely cure chronic hepatitis B infection, highlighting the need for new anti-HBV drugs. Nucleic acid polymers (NAPs) are phosphorothioated oligonucleotides that have demonstrated a great potential to inhibit infection with several viruses. In chronically infected human patients, NAPs administration lead to a decline of blood HBsAg and HBV DNA and to HBsAg seroconversion, the expected signs of functional cure. NAPs have also been shown to prevent infection of duck hepatocytes with the Avihepadnavirus duck hepatitis B virus (DHBV) and to exert an antiviral activity against established DHBV infection in vitro and in vivo. In this study, we investigated the specific anti-HBV antiviral activity of NAPs in the HepaRG human hepatoma cell line and primary cultures of human hepatocytes. NAPs with different chemical features (phosphorothioation, 2'O-methyl ribose, 5-methylcytidine) were assessed for antiviral activity when provided at the time of HBV inoculation or post-inoculation. NAPs dose-dependently inhibited HBV entry in a phosphorothioation-dependent, sequence-independent and size-dependent manner. This inhibition of HBV entry by NAPs was impaired by 2'O-methyl ribose modification. NAP treatment after viral inoculation did not elicit any antiviral activity.http://europepmc.org/articles/PMC5479567?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Clément Guillot Nora Martel Françoise Berby Isabelle Bordes Olivier Hantz Matthieu Blanchet Camille Sureau Andrew Vaillant Isabelle Chemin |
spellingShingle |
Clément Guillot Nora Martel Françoise Berby Isabelle Bordes Olivier Hantz Matthieu Blanchet Camille Sureau Andrew Vaillant Isabelle Chemin Inhibition of hepatitis B viral entry by nucleic acid polymers in HepaRG cells and primary human hepatocytes. PLoS ONE |
author_facet |
Clément Guillot Nora Martel Françoise Berby Isabelle Bordes Olivier Hantz Matthieu Blanchet Camille Sureau Andrew Vaillant Isabelle Chemin |
author_sort |
Clément Guillot |
title |
Inhibition of hepatitis B viral entry by nucleic acid polymers in HepaRG cells and primary human hepatocytes. |
title_short |
Inhibition of hepatitis B viral entry by nucleic acid polymers in HepaRG cells and primary human hepatocytes. |
title_full |
Inhibition of hepatitis B viral entry by nucleic acid polymers in HepaRG cells and primary human hepatocytes. |
title_fullStr |
Inhibition of hepatitis B viral entry by nucleic acid polymers in HepaRG cells and primary human hepatocytes. |
title_full_unstemmed |
Inhibition of hepatitis B viral entry by nucleic acid polymers in HepaRG cells and primary human hepatocytes. |
title_sort |
inhibition of hepatitis b viral entry by nucleic acid polymers in heparg cells and primary human hepatocytes. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2017-01-01 |
description |
Hepatitis B virus (HBV) infection remains a major public health concern worldwide with 240 million individuals chronically infected and at risk of developing cirrhosis and hepatocellular carcinoma. Current treatments rarely cure chronic hepatitis B infection, highlighting the need for new anti-HBV drugs. Nucleic acid polymers (NAPs) are phosphorothioated oligonucleotides that have demonstrated a great potential to inhibit infection with several viruses. In chronically infected human patients, NAPs administration lead to a decline of blood HBsAg and HBV DNA and to HBsAg seroconversion, the expected signs of functional cure. NAPs have also been shown to prevent infection of duck hepatocytes with the Avihepadnavirus duck hepatitis B virus (DHBV) and to exert an antiviral activity against established DHBV infection in vitro and in vivo. In this study, we investigated the specific anti-HBV antiviral activity of NAPs in the HepaRG human hepatoma cell line and primary cultures of human hepatocytes. NAPs with different chemical features (phosphorothioation, 2'O-methyl ribose, 5-methylcytidine) were assessed for antiviral activity when provided at the time of HBV inoculation or post-inoculation. NAPs dose-dependently inhibited HBV entry in a phosphorothioation-dependent, sequence-independent and size-dependent manner. This inhibition of HBV entry by NAPs was impaired by 2'O-methyl ribose modification. NAP treatment after viral inoculation did not elicit any antiviral activity. |
url |
http://europepmc.org/articles/PMC5479567?pdf=render |
work_keys_str_mv |
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