Inhibition of the hepatitis B virus replication in vitro by an oligodeoxynucleotide containing cytidine-guanosine motifs

Li, Ning; Fan, Xue‐Gong; Chen, Zhaohui; Zhu, Changtai; Liu, Hongbo; Huang, Yan

doi:10.1016/j.imlet.2005.06.023

Cited by 6 publications

(4 citation statements)

References 47 publications

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“…The antiviral effect of CpG-induced cytokines, using SN PBMC CpG 2216, was demonstrated by 73% and 82% inhibition of intracellular encapsidated HBV DNA in HepG2-and HepaRG-transduced cells, respectively (Figure 1A). Such a powerful and significant (P<0.001) inhibition was obtained using several concentrations of IFN-α induced by CpG stimulation (200-1,000 pg) and is similar to a previous study using HepG2.2.15 cells [8]. IFN-α has been shown to inhibit HBV replication by eliminating viral RNA-containing capsids in the cytoplasm of hepatocytes [9].…”

Section: Resultssupporting

confidence: 86%

Inhibitory effect of the combination of CpG-induced cytokines with lamivudine against hepatitis B virus replication in vitro

et al. 2009

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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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Section: Resultssupporting

confidence: 86%

Inhibitory effect of the combination of CpG-induced cytokines with lamivudine against hepatitis B virus replication in vitro

et al. 2009

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“…This indicates that CpG ODN is an effective anti-hepatitis virus agent. Some in vitro studies demonstrated that the treatment of CpG ODN could stimulate the production of cytokines by peripheral blood mononuclear cells and inhibit HBV DNA replication and the secretion of HBsAg and HBeAg in HepG2 2.2.15 cells [30], or could reduce the effective concentrations of lamivudine for in vitro anti-HBV treatment when used with CpG ODNs together [31].…”

Section: Discussionmentioning

confidence: 99%

CpG Oligodeoxynucleotide Inhibits HBV Replication in a Hydro Dynamic Injection Murine Model

Huang

Zhang

et al. 2014

Antiviral Therapy

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“…To date, different strategies have been tried in enhancing HBV‐specific CTL responses, including CpG DNA, heat‐shock proteins, DNA vaccines and various epitope or protein vaccines 2,6–9 . DNA vaccines were shown to elicit both humoral and cellular immune responses in small animal models; however, this method has achieved limited success in large non‐human primates 6,10 .…”

Section: Introductionmentioning

confidence: 99%

Hepatitis B virus core antigen epitopes presented by HLA‐A2 single‐chain trimers induce functional epitope‐specific CD8⁺ T‐cell responses in HLA‐A2·1/Kb transgenic mice

Zhang

Shan

et al. 2007

Immunology

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Summary The potency of CD8+ cytotoxic T lymphocyte (CTL) responses toward core antigen has been shown to affect the outcomes of hepatitis B virus (HBV) infection. Since single‐chain trimers (SCT) composed of peptide epitope β2‐microglobulin (β2m) and major histocompatiblity complex (MHC) class I heavy chain covalently linked together in a single molecule have been shown to stimulate efficient CTL responses, we investigated the properties of human leucocyte antigen (HLA)‐A2 SCTs encoding the HBV core antigen (HBcAg) epitopes C18−27 and C107−115. Transfection of NIH‐3T3 cells with pcDNA3.0‐SCT‐C18−27 and SCT‐C107−115 leads to stable presentation of HBcAg epitopes at the cell surface. HLA‐A2.1/Kb transgenic mice vaccinated with the SCT constructs, either as a DNA vaccine alone or followed by a boost with recombinant vaccinia virus, were shown to generate HBcAg‐specific CTL responses by enzyme‐linked immunospot assay (ELISPOT) and in vitro interferon‐γ release experiments. HBcAg‐specific CTLs from vaccinated HLA‐A2.1/Kb transgenic mice were able to inhibit HBV surface and e antigen expression as indicated by HepG2.2.15 cells. Our data indicate that a DNA vaccine encoding a human HLA‐A2 SCT with HBV epitopes can lead to stable, enhanced HBV core antigen presentation, and may be useful for the control of HBV infection in HLA‐A2‐positive HBV carriers.

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Inhibition of the hepatitis B virus replication in vitro by an oligodeoxynucleotide containing cytidine-guanosine motifs

Cited by 6 publications

References 47 publications

Inhibitory effect of the combination of CpG-induced cytokines with lamivudine against hepatitis B virus replication in vitro

Inhibitory effect of the combination of CpG-induced cytokines with lamivudine against hepatitis B virus replication in vitro

CpG Oligodeoxynucleotide Inhibits HBV Replication in a Hydro Dynamic Injection Murine Model

Hepatitis B virus core antigen epitopes presented by HLA‐A2 single‐chain trimers induce functional epitope‐specific CD8⁺ T‐cell responses in HLA‐A2·1/Kb transgenic mice

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Inhibition of the hepatitis B virus replication in vitro by an oligodeoxynucleotide containing cytidine-guanosine motifs

Cited by 6 publications

References 47 publications

Inhibitory effect of the combination of CpG-induced cytokines with lamivudine against hepatitis B virus replication in vitro

Inhibitory effect of the combination of CpG-induced cytokines with lamivudine against hepatitis B virus replication in vitro

CpG Oligodeoxynucleotide Inhibits HBV Replication in a Hydro Dynamic Injection Murine Model

Hepatitis B virus core antigen epitopes presented by HLA‐A2 single‐chain trimers induce functional epitope‐specific CD8+ T‐cell responses in HLA‐A2·1/Kb transgenic mice

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Hepatitis B virus core antigen epitopes presented by HLA‐A2 single‐chain trimers induce functional epitope‐specific CD8⁺ T‐cell responses in HLA‐A2·1/Kb transgenic mice