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Inhibition of the HCV core protein on the immune response to HBV surface antigen and on HBV gene expression and replication in vivo.

ABSTRACT: The hepatitis C virus (HCV) core protein is a multifunctional protein that can interfere with the induction of an immune response. It has been reported that the HCV core protein inhibits HBV replication in vitro. In this study, we test the effect of the HCV core gene on the priming of the immune response to hepatitis B surface antigen (HBsAg) and on the replication of HBV in vivo. Our results showed that the full-length HCV core gene inhibits the induction of an immune response to the heterogeneous antigen, HBsAg, at the site of inoculation when HCV core (pC191) and HBsAg (pHBsAg) expression plasmids are co-administered as DNA vaccines into BALB/c mice. The observed interference effect of the HCV core occurs in the priming stage and is limited to the DNA form of the HBsAg antigen, but not to the protein form. The HCV core reduces the protective effect of the HBsAg when the HBsAg and the HCV core are co-administered as vaccines in an HBV hydrodynamic mouse model because the HCV core induces immune tolerance to the heterogeneous HBsAg DNA antigen. These results suggest that HCV core may play an important role in viral persistence by the attenuation of host immune responses to different antigens. We further tested whether the HCV core interfered with the priming of the immune response in hepatocytes via the hydrodynamic co-injection of an HBV replication-competent plasmid and an HCV core plasmid. The HCV core inhibited HBV replication and antigen expression in both BALB/c (H-2d) and C57BL/6 (H-2b) mice, the mouse models of acute and chronic hepatitis B virus infections. Thus, the HCV core inhibits the induction of a specific immune response to an HBsAg DNA vaccine. However, HCV C also interferes with HBV gene expression and replication in vivo, as observed in patients with coinfection.

SUBMITTER: Zhu W

PROVIDER: S-EPMC3443233 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Inhibition of the HCV core protein on the immune response to HBV surface antigen and on HBV gene expression and replication in vivo.

Zhu Wenbo W Wu Chunchen C Deng Wanyu W Pei Rongjun R Wang Yun Y Cao Liang L Qin Bo B Lu Mengji M Chen Xinwen X

PloS one 20120914 9

The hepatitis C virus (HCV) core protein is a multifunctional protein that can interfere with the induction of an immune response. It has been reported that the HCV core protein inhibits HBV replication in vitro. In this study, we test the effect of the HCV core gene on the priming of the immune response to hepatitis B surface antigen (HBsAg) and on the replication of HBV in vivo. Our results showed that the full-length HCV core gene inhibits the induction of an immune response to the heterogene ...[more]

PMID: 23024803

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Project description:BackgroundThe measurement of hepatitis C virus core antigen (HCV-coreAg) has been shown to be an indicator of active HCV infection. The aim of the present study was 1) to investigate the stability and effectiveness of HCV-coreAg and HCV-RNA quantification in HCV infection with or without HIV-1 coinfection, 2) to explore the association between the HCV-coreAg/HCV-RNA (Ag/RNA) ratio and the immune status in chronic HCV/HIV-1-coinfected patients.MethodsA longitudinal investigation comprised of 227 HCV-monoinfected (n = 129) and HCV/HIV-1-coinfected (n = 98) patients was initiated in August 2009, and 139 (73 with HCV monoinfection and 66 with HCV/HIV-1 coinfection) were followed up in August 2012. Both HCV core antigen and HCV RNA quantification were determined on this cryopreserved plasma. HCV core antigen and HCV RNA quantification were performed subsequently. In addition, an in vitro experiment investigating the possibility of degradation of HCV components (core antigen and RNA) were conducted.ResultsSignificant and stable correlations (p < 0.001) were observed both in chronic HCV-monoinfected and HCV/HIV-1-coinfected patients over the 3-year observation. Coinfected patients with immunocompromised condition had a significantly higher (p < 0.05) Ag/RNA ratios than those patients with immunocompetent condition both at two time points (2009 and 2012). Moreover, the Ag/RNA ratios were negatively correlated with CD4+ T-cell counts (p < 0.001). An in vitro experiment investigated the possibility of the slower degradation of HCV particles under HIV-related immunocompromised condition was conducted and the data demonstrated that the Ag/RNA ratios were significantly higher in HIV-1-positive plasma than in healthy plasma (p = 0.005) in this study.ConclusionsOur longitudinal study indicated that the HCV-coreAg presented comparable dynamics over time as HCV RNA in chronic HCV-infected patients. Meanwhile, the HCV-coreAg/HCV-RNA ratio was closely associated with immune status in HCV/HIV-1-coinfected patients.

Project description:BackgroundThus far, few studies have investigated the safety and efficacy of programmed death-1 (PD-1) immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) antibodies in patients with hepatitis B virus (HBV)-related liver cancer.ObjectiveTo investigate the effect of combination therapy with programmed death-1 (PD-1) immune checkpoint inhibitors (ICIs) and tyrosine kinase inhibitors (TKIs) on HBV-related liver cancer.MethodsUntil January 31, 2022, liver cancer patients with hepatitis B surface antigen (HBsAg) or HBV DNA positivity, treated with PD-1 ICIs and TKIs combined with nucleoside analogs (NAs), were retrospectively reviewed. The correlation between the change in HBV DNA and HBsAg levels and tumor response was analyzed using the χ2 test. Cox univariate and multivariate survival analyses and Kaplan-Meier curves were used to identify and compare risk factors and overall survival (OS).ResultsA total of 48 patients were enrolled in the study, with an objective response rate (ORR) of 31.3%, a disease control rate (DCR) of 66.7%; the incidence of adverse events was mostly mild. A significant decrease in HBV DNA and HBsAg levels was observed at 12 and 24 weeks compared with the baseline (p < 0.05). Compared to patients with progressive disease (PD), patients with disease control showed a more significant decrease in HBV DNA and HBsAg levels at 12 and 24 weeks (p < 0.001). Eleven patients showed elevations in HBV DNA level and one of them showed HBV reactivation; however, the reactivation was not associated hepatitis. Moreover, eight patients showed elevation in HBsAg. Elevation in HBV DNA level was associated with poor tumor response (P=0.001, OR=18.643 [95% CI: 3.271-106.253]). Cox survival analysis suggested that HBV DNA increase (P=0.011, HR=4.816, 95% CI: 1.439-16.117) and HBsAg increase (P=0.022, HR=4.161, 95% CI: 1.224-16.144) were independent risk factors associated with survival time. Kaplan-Meier curves suggested that patients who exhibited an increase in HBV DNA (6.87 months vs undefined, log-rank test: p= 0.004) and HBsAg (8.07 months vs undefined, log-rank test: p= 0.004) levels had a shorter median survival time (MST). Patients without increased HBsAg showed better baseline liver function and routine blood tests (p<0.05) than patients with increased HBsAg. An increase in C-reactive protein (CRP) and interleukin-6 (IL-6), and a decrease in T lymphocytes, CD4+ T lymphocytes, and B lymphocytes at 1-week post-treatment associated with HBsAg well-controlled.ConclusionHBV-related liver cancer patients treated with combination therapy showed improved efficacy and safety profiles. Combination therapy has some effect on HBV infection, and a correlation between tumor response and antiviral efficacy was found. Elevation of HBV DNA and HBsAg levels may indicate poorer tumor response and survival time. Better baseline liver function and early immune activation may be associated with decline in HBsAg levels.

Dataset Information

Inhibition of the HCV core protein on the immune response to HBV surface antigen and on HBV gene expression and replication in vivo.

Publications

Inhibition of the HCV core protein on the immune response to HBV surface antigen and on HBV gene expression and replication in vivo.

Similar Datasets

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