Suppression of hepatitis B virus enhancer 1 and 2 by hepatitis C virus core protein

Schüttler, Christian G.; Fiedler, Nicola; Schmidt, Katja; Repp, Reinald; Gerlich, Wolfram H.; Schaefer, Stephan

doi:10.1016/s0168-8278(02)00296-9

Cited by 153 publications

(119 citation statements)

References 38 publications

Supporting

Mentioning

111

Contrasting

Unclassified

Order By: Relevance

“…The HCV core protein is a part of the viral capsid, and it inhibits HBV replication and gene expression and suppresses activity of HBV enhancers (45,234). Chen et al elucidated several mechanisms of HCV core protein-mediated suppression of HBV (45).…”

Section: Coinfection With Other Microbesmentioning

confidence: 99%

Molecular Mechanisms Underlying Occult Hepatitis B Virus Infection

2012

View full text Add to dashboard Cite

SUMMARY Chronic hepatitis B virus (HBV) infection is a complex clinical entity frequently associated with cirrhosis and hepatocellular carcinoma (HCC). The persistence of HBV genomes in the absence of detectable surface antigenemia is termed occult HBV infection. Mutations in the surface gene rendering HBsAg undetectable by commercial assays and inhibition of HBV by suppression of viral replication and viral proteins represent two fundamentally different mechanisms that lead to occult HBV infections. The molecular mechanisms underlying occult HBV infections, including recently identified mechanisms associated with the suppression of HBV replication and inhibition of HBV proteins, are reviewed in detail. The availability of highly sensitive molecular methods has led to increased detection of occult HBV infections in various clinical settings. The clinical relevance of occult HBV infection and the utility of appropriate diagnostic methods to detect occult HBV infection are discussed. The need for specific guidelines on the diagnosis and management of occult HBV infection is being increasingly recognized; the aspects of mechanistic studies that warrant further investigation are discussed in the final section.

show abstract

Section: Coinfection With Other Microbesmentioning

confidence: 99%

Molecular Mechanisms Underlying Occult Hepatitis B Virus Infection

2012

View full text Add to dashboard Cite

show abstract

“…These observations may also explain the phenomenon why occult HBV infection is frequently found in patients with chronic hepatitis B superimposed by acute HCV infection in HBV endemic areas. In vitro studies consistently revealed that HCV is capable of suppressing HBV replication, and this inhibitory effect is possibly mediated by HCV core protein acting on HBV enhancer activity [31][32][33][34]. Nevertheless, conflicting results with respect to the effects of HCV core and NS5A proteins on the level of HBV replication have been reported [34][35][36][37].…”

Section: Viral Interactions Between Hbv and Hcv And Their Impact On Tmentioning

confidence: 99%

Dual chronic hepatitis B virus and hepatitis C virus infection

Liu

Chen

2009

Hepatol Int

View full text Add to dashboard Cite

Dual hepatitis B virus (HBV) and hepatitis C virus (HCV) infection are common in HBV or HCV endemic areas. However, several clinical and pathogenetic issues remain unresolved. First, clinical and in vitro studies suggest the interactions between two viruses. The dynamics of the interaction in untreated setting versus treated setting and its influence on the long-term outcomes await further studies. A key issue regarding viral interactions is whether modulation of infection occurs in the same dually infected individual hepatocyte of the liver. Clarifying this issue may help to understand the reciprocal interference between HCV and HBV and provide clues for future immunopathogenetic studies. Second, the prevalence and clinical significance of coexisting occult HBV infection in patients with chronic HCV infection need further investigations. Third, combination therapy of peginterferon alfa2a and ribavirin appears to be just as effective and safe for the treatment of hepatitis B surface antigen (HBsAg)-positive patients chronically infected with active chronic hepatitis C as it is in patients with HCV monoinfection. Nevertheless, one-third of dually infected patients with nondetectable serum HBV DNA-level pretreatment developed HBV reactivation posttreatment. How to prevent and treat this reactivation should be clarified. Furthermore, about 10% of the dually infected patients lost HBsAg. Underlying mechanisms await further investigations. Finally, the optimal treatment strategies for dually infected patients with hepatitis B e antigen-positive chronic hepatitis B should be identified in future clinical trials.

show abstract

“…This inhibition may be mediated by the host immune response (via the induction of cytokines such as interferons) or by a direct effect of HCV proteins. In this regard, it has been shown that HCV core and NS2 proteins inhibit HBV replication and gene expression in vitro (4,5,19,21,22).Direct interference mediated by HCV proteins can occur in vivo only if both HBV and HCV coexist in the same hepatocyte. However, it has not been demonstrated whether HBV and HCV infect the same cell in the liver of patients coinfected with the two viruses.…”

mentioning

confidence: 99%

mentioning

confidence: 99%

Hepatitis C Virus (HCV) and Hepatitis B Virus (HBV) Can Coinfect the Same Hepatocyte in the Liver of Patients with Chronic HCV and Occult HBV Infection

Rodríguez‐Iñigo

Bartolomé

Ortiz‐Movilla

et al. 2005

J Virol

View full text Add to dashboard Cite

In this work, we have shown that hepatitis C virus (HCV) and hepatitis B virus (HBV) can coexist in the same hepatocyte using double fluorescent in situ hybridization in liver biopsy samples from patients with chronic HCV infection with occult HBV infection. Digital image analysis of hybridization signals showed that the HBV DNA levels in coinfected hepatocytes were lower than those in cells infected only with HBV. This finding supports the hypothesis of inhibition of HBV replication by HCV. Furthermore, HCV RNA levels were lower in coinfected cells than in cells infected only with HCV, suggesting that HBV may also inhibit HCV replication.Hepatitis B virus (HBV) belongs to the Hepadnaviridae family of animal viruses, and its genome consists of a circular partially double-stranded DNA molecule of 3.2 kb in length which contains four overlapping reading frames that code for surface proteins (HBsAg), core proteins (HBc/HBeAg), the viral polymerase, and the transcriptional transactivator X protein (HBx) (9).Hepatitis C virus (HCV) is classified in the Hepacivirus genus of the Flaviviridae family, and its genome is a positive-stranded RNA of 9.6 kb in length that encodes a large polyprotein that undergoes proteolytic processing by cellular and viral proteinases to generate the individual viral proteins (17).As HBV and HCV share similar transmission routes, coinfection with the two viruses is not a rare event (3,6,7). Clinical data obtained from chronic HBV carriers superinfected with HCV suggest that HCV may inhibit HBV replication (13,15,20). This hypothesis is supported by the fact that patients with chronic HCV infection frequently have a special form of HBV infection, termed occult HBV infection (2,8,10,12). This is characterized by the presence of low levels of HBV DNA in serum and/or in liver in the absence of detectable HBsAg in serum. This inhibition may be mediated by the host immune response (via the induction of cytokines such as interferons) or by a direct effect of HCV proteins. In this regard, it has been shown that HCV core and NS2 proteins inhibit HBV replication and gene expression in vitro (4,5,19,21,22).Direct interference mediated by HCV proteins can occur in vivo only if both HBV and HCV coexist in the same hepatocyte. However, it has not been demonstrated whether HBV and HCV infect the same cell in the liver of patients coinfected with the two viruses. To address this issue, we have used double fluorescent in situ hybridization to determine the presence of HBV DNA and HCV RNA in liver biopsy samples from six patients with chronic hepatitis C (anti-HCV positive, serum HCV RNA positive) and occult HBV infection (HBsAg negative, serum HBV DNA positive).Patients underwent a liver biopsy for diagnostic purposes. After liver samples were obtained, they were divided into two portions. One fragment was processed for histological diagnosis and for in situ hybridization, and the other was embedded in RNAlater (QIAGEN, Hilden, Germany) in less than 30 seconds after being obtained and stored at Ϫ20°C. At th...

show abstract

Suppression of hepatitis B virus enhancer 1 and 2 by hepatitis C virus core protein

Cited by 153 publications

References 38 publications

Molecular Mechanisms Underlying Occult Hepatitis B Virus Infection

Molecular Mechanisms Underlying Occult Hepatitis B Virus Infection

Dual chronic hepatitis B virus and hepatitis C virus infection

Hepatitis C Virus (HCV) and Hepatitis B Virus (HBV) Can Coinfect the Same Hepatocyte in the Liver of Patients with Chronic HCV and Occult HBV Infection

Contact Info

Product

Resources

About