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P0556
ANTIVIRAL EFFECTS OF NUCLEIC ACID POLYMERS ON
HEPATITIS B VIRUS INFECTION
C. Guillot1, O. Hantz1, A. Vaillant2, I. Chemin1. 1Cancer Research
Center of Lyon UMR Inserm 1052 CNRS 5286, Lyon, France; 2REPLICor
Inc., Montreal, Canada
E-mail: [email protected]
Background and Aims: Hepatitis B virus (HBV) infection remains
a major public health problem worldwide and current therapies
are rarely able to cure HBV infection. Nucleic acid polymers
(NAPs) have been shown to inhibit duck HBV infection in vitro
and in vivo (Noordeen et al., 2013). NAPs have been shown
to eliminate the hepatitis B surface antigen (HBsAg) from the
blood (in ducks infected with the duck hepatitis B virus) but the
mechanism whereby NAPs achieve the removal of surface antigen
from the blood has yet to be clearly elucidated. Due to their
phosphorothioate oligonucleotide structure, NAPs are chemically
analogous to sulfated polyglycans such as heparin which are known
to block entry of hepatitis B virus. In this study we investigated the
in vitro antiviral activity of NAPs in HBV infected HepaRG cells and
primary human hepatocytes.
Methods: NAP uptake into cells was assessed using Cy3 labeled
NAPs. In order to evaluate potent effects of NAPs on HBV entry as
well as post-entry, HBV infected differentiated HepaRG cells and
primary human hepatocytes were treated with NAPs every two
days starting at the time of infection or starting two days postinfection.
The Elecsys HBsAg II quant automated system was used
to quantitatively measure the secreted HBsAg. PreS1 containing
particles were also assessed by ELISA and extracellular HBVDNA
was measured by real-time PCR.
Results: Fluorescent NAPs were observed to enter into
differentiated HepaRG cells and in primary cultures more
particularly in hepatocytes rather than biliary cells. 5mM and 1mM
NAPs significantly reduced extracellular HBsAg by 80% and 40%
respectively as well as PreS1 containing particles when added at the
time of infection. Interestingly, 5mM NAPs seems also to decrease
extracellular HBsAg by 25% as well as PreS1 containing particles
when added two days post-infection, suggesting NAPs exert a postentry
antiviral effect.
Conclusions: In this study, we showed a strong antiviral activity
of nucleic acid polymers against HBV infection in HepaRG cells
and primary human hepatocytes. Our results suggest that NAPs
are able to block entry of HBV but also to have an effect on the
replication cycle following entry of the virus which results in a
reduction of HBsAg released into the supernatant. These antiviral
activities both on virus entry and within the cells promise a strong
potential of NAPs alone or in combination with already existing
antiviral treatments.
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发表于 2015-5-2 05:51