Inhibitory effect of the combination of CpG-induced cytokines with lamivudine against hepatitis B virus replication in vitro.
Antivir Ther
; 14(1): 131-5, 2009.
Article
in En
| MEDLINE
| ID: mdl-19320247
ABSTRACT
BACKGROUND:
Currently approved antiviral monotherapies against chronic hepatitis B fail to eradicate hepatitis B virus (HBV), to overcome the defects in HBV-specific immune responses and to prevent HBV relapse after cessation of therapy. CpG oligodesoxynucleotides (CpG ODN) are synthetic agonists of Toll-like receptor 9 and potent inducers of innate and acquired immunity. Our aim was to establish the proof of concept of the antiviral benefit of combining a nucleoside analogue with CpG-induced cytokines on HBV replication in vitro.METHODS:
Peripheral blood mononuclear cells from HBV-negative individuals were stimulated with CpG ODN to generate CpG-induced cytokine supernatants. Proliferating HepaRG and HepG2 cells were transduced with recombinant HBV baculovirus and differentiated HepaRG cells were inoculated with HBV virions. Antiviral effects of CpG-induced cytokine with or without lamivudine were evaluated by analysing HBV DNA, HBV RNA and antigen secretion (hepatitis B surface antigen [HBsAg] and hepatitis B e antigen [HBeAg]).RESULTS:
Following transduction or HBV inoculation, CpG-induced cytokines strongly inhibited HBV viral intermediates of replication, as well as HBsAg and HBeAg secretion from infected cells. Strikingly, in transduced HepaRG cells, the combination of CpG-induced cytokines with lamivudine reduced the 50% effective concentration of lamivudine by 100-fold. Importantly, the treatment of CpG-induced cytokines prior to HBV inoculation conferred a partial protection against infection to hepatocytes.CONCLUSIONS:
CpG-induced cytokines associated with polymerase inhibitors represent a promising combination to suppress HBV replication. Such an immunotherapeutic strategy should be evaluated in vivo to assess restoration and duration of anti-HBV-specific immune responses.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Oligodeoxyribonucleotides
/
Virus Replication
/
DNA, Viral
/
RNA, Viral
/
Hepatitis B virus
/
Lamivudine
Limits:
Humans
Language:
En
Journal:
Antivir Ther
Journal subject:
TERAPIA POR MEDICAMENTOS
/
VIROLOGIA
Year:
2009
Type:
Article
Affiliation country:
France