Lack ofin vivo activation of the interferon system in HBsAg-positive chronic active hepatitis

Poitrine, A; Chousterman, S.; Chousterman, M; Naveau, Sylvie; Thang, M.N.; Chaput, Jean‐Claude

doi:10.1002/hep.1840050202

Cited by 68 publications

(22 citation statements)

References 14 publications

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“…This result, together with previous studies, suggests that the HBc protein might modulate the expression of genes implicated in the antiviral and\or antiproliferative activity of IFN. This would fit with the in vivo and in vitro reciprocal interaction between IFN and HBV, as described previously (Ikeda et al, 1986 ;Jakschies et al, 1993 ;Nishiguchi et al, 1989 ;Onji et al, 1989 ;Poitrine et al, 1985). Our results are also consistent with our previous in vivo observations that suggest a role for dHBV DNA in the mechanism of HBV persistence.…”

Section: Discussionsupporting

confidence: 82%

“…However, after IFN treatment, only about 30-40 % of patients show clearance of HBV replication markers, normalization of transaminases and improvement in liver histology (Perrillo et al, 1990). Several in vivo studies have shown a lack of activation of the IFN system in patients with acute or chronic hepatitis B (Ikeda et al, 1986 ;Jakschies et al, 1993 ;Nishiguchi et al, 1989 ;Poitrine et al, 1985). In addition, previous in vitro studies have suggested that HBV DNA might play a direct role in the development of resistance to endogenous or exogenous IFN.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Inhibition of interferon-inducible MxA protein expression by hepatitis B virus capsid protein.

Rosmorduc

Sirma

Soussan

et al. 1999

Journal of General Virology

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Section: Discussionsupporting

confidence: 82%

Section: Introductionmentioning

confidence: 99%

Inhibition of interferon-inducible MxA protein expression by hepatitis B virus capsid protein.

Rosmorduc

Sirma

Soussan

et al. 1999

Journal of General Virology

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“…The patients who develop HBV chronic infection present an inadequate immune function with respect to alpha-IFN, interleukin 2 (IL-2), major histocompatibility gene complex class I antigen display, and the 2Ј5Ј oligoadenylate synthetase system [Poitrine et al, 1985;Ikeda et al, 1986;Chu et al, 1987;Anastassakos et al, 1988].…”

Section: Introductionmentioning

confidence: 99%

Double-blind, randomized controlled trial of interleukin-2 treatment of chronic hepatitis B

et al. 1998

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Pilot studies have demonstrated that recombinant interleukin 2 (rIL-2) has an indirect antiviral activity against hepatitis B virus, but the minimal dose of rIL-2 for induction of this effect was not defined. The aim of the study was to ascertain the most efficient dose of rIL-2 for induction of the loss of detectable serum HBV-DNA or a 50% or greater decrease in its level. Thirty-one patients with chronic hepatitis B, hepatitis B e antigen and serum HBV-DNA positive were enrolled in this double-blind randomized controlled trial. Patients were divided: Group I (n = 8) placebo; Group II (n = 7) treated with 0.9 MU of rIL-2 subcutaneously administered daily for 8 weeks; Group III (n = 8) treated with 1.8 MU of rIL-2 under the same schedule; Group IV (n = 8) which received 3.6 MU of rIL-2 under the same conditions. At the end of treatment 25% of the patients in the placebo group, and 13% and 25% in rIL-2 groups III and IV, respectively, had a decrease in HBV-DNA higher than 50% of the basal value. None of the patients lost serum HBV-DNA. Only three patients (one from group II and two from group IV) normalized the ALT levels. Overall, during treatment, ALT levels decreased in the treated groups. This decrease occurred simultaneously with an increase in serum HBV-DNA concentration. Since the response rate in the treated groups was similar to that of the placebo group, rIL-2 is not useful as monotherapy for the treatment of chronic hepatitis B at the doses and schedules used in this study.

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“…Individuals chronically infected with HBV exhibit a poor response in the production of interferon and of interferoninducible enzymes (12)(13)(14)(15)(16)(17). In this paper, evidence is provided that indicates a potential molecular basis for such responses.…”

Section: Discussionmentioning

confidence: 92%

“…Interferon has been detected in serum of patients with a variety of viral illnesses but not in many individuals exhibiting chronic HBV infections (12)(13)(14)(15)(16). Evaluation of the interferon response by measuring the activity of the interferon-inducible enzyme (2'-5')oligoadenylate synthetase also suggests that poor activation of the interferon system exists in chronic HBV carriers (17). Furthermore, a lack of production of interferon in peripheral blood mononuclear cells that were either stimulated in vitro with plant lectins or infected with viruses also indicates a defect in the expression of interferon in chronic HBV carriers (12).…”

Section: Introductionmentioning

confidence: 99%

Hepatitis B virus suppresses expression of human beta-interferon.

Twu

Lee

Lin

et al. 1988

Proc. Natl. Acad. Sci. U.S.A.

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To determine whether hepatitis B virus (HBV) regulates the expression of the human fl-interferon gene, a series of recombinant bovine papilloma virus plasmids containing the human interferon gene and various fragments of the HBV genome were constructed and used to transform C127 cells, a murine fibroblast line. Analysis of the DNA from transformed C127 cells indicated that the interferon gene was intact and that the plasmids replicated as stable multicopy elements. The 1828-base-pair BamHI HBV DNA fragment containing the core antigen gene, but not the 2755-base-pairBgl II HBV DNA fragment encoding both the surface antigen and the X antigen, suppressed the production of human fl-interferon. No effect by any of the recombinant plasmids on the synthesis of murine interferon was detected. The suppression of human f-interferon by HBV occurs via a trans-acting factor.A frameshift mutation within the HBV core gene alleviates the inhibitory activity; thus we infer that the core protein is this factor or is crucially associated with this activity. was cloned into the same BamHI site of the plasmid pdBPV-1, which had one of the two BamHI sites destroyed (19). The resulting plasmids, pBHC and pBHS (Fig. 1), were used in further plasmid constructions. The plasmid pIFR containing the human Pinterferon gene as a 1.6-kilobase (kb) EcoRI-HindIII fragment (20) was linearized by digestion with EcoRI and the EcoRI ends were converted to HindIII ends. Following digestion with HindIII, the resulting 1.6-kb HindIII fragment containing the human 8-interferon gene was isolated and inserted into the HindIII site of (i) pdBPV-1, (it) pBHS, and (iii) pBHC, resulting in the formation of pBI, pBHSI, and pBHCI, respectively (Fig. 1).An insertion mutation at the Taq I site (mp 2014) that is within the HBV core antigen gene was created by digesting circularized 1828-bp BamHI HBV DNA fragments with Taq I. The linearized fragment was filled-in, ligated, and then cleaved with BamHI. The resulting BamHI HBV DNA fragment then was cloned into the BamHI site of pBI, yielding pBIHCdTaqI. The insertion mutation resulted in the destruction ofthe Taq I site in the HBV core antigen gene and in a shift in the open reading frame.Cell Cultures and DNA Transfections. Murine C127 fibroblasts were grown as described (20). One day before transfection, 8 x 104 cells were plated in each well of a 24-well plate; the cells were refed with fresh medium 4 hr before transfection. C127 cells were transfected by the calcium phosphate precipitation technique (21) with 0.2 Ag of total plasmid DNA that included 50 ng of a plasmid containing the neomycin-resistance gene. Eight hours after transfection, cells were diluted and G418 (600 ,ug/ml) was added. After 14-21 days, well-separated foci were picked and stable transformants were grown to confluence in the presence of G418.Interferon Induction and Assay. Induction of interferon by poly(I)-poly(C) in C127 cells that had been confluent for 4 days was performed as described (20). Uninduced cells were treated in t...

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Lack ofin vivo activation of the interferon system in HBsAg-positive chronic active hepatitis

Cited by 68 publications

References 14 publications

Inhibition of interferon-inducible MxA protein expression by hepatitis B virus capsid protein.

Inhibition of interferon-inducible MxA protein expression by hepatitis B virus capsid protein.

Double-blind, randomized controlled trial of interleukin-2 treatment of chronic hepatitis B

Hepatitis B virus suppresses expression of human beta-interferon.

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