Hepatitis B virus and hepatitis C virus interaction in Huh-7 cells

Infectious Diseases Laboratories, Institute of Medical and Veterinary Sciences, Adelaide, SA, Australia.
Journal of Hepatology (Impact Factor: 11.34). 07/2009; 51(3):446-57. DOI: 10.1016/j.jhep.2009.04.025
Source: PubMed


Co-infection with hepatitis B virus (HBV) and hepatitis C virus (HCV) increases the risk of development and the severity of chronic liver disease. Although dominant and suppressive effects of each virus over the other have been reported in vivo, in vitro studies of HBV/HCV co-infection have been limited to analysis of the effects of over-expression of HCV proteins on HBV replication.
We have re-examined HBV/HCV interactions in Huh-7 cells following co-infection with cell culture-propagated HCV (HCVcc; genotype 2a) and a recombinant adenovirus vector capable of delivering a replication-competent HBV genome (AdHBV; genotype A).
While intracellular HCV RNA levels were significantly increased when cells were pre-infected with AdHBV, HCV replication and virion secretion were not altered by simultaneous infection with AdHBV or AdHBV superinfection of HCV-infected cells. Likewise intracellular and secreted HBV DNA levels and HBV promoter activities were either unchanged or modestly increased by HCVcc infection. Despite this, HCV E2 and HBsAg proteins colocalized extensively in co-infected cells suggesting shared stages in viral egress.
These studies indicate that there is little direct interaction of HBV and HCV in co-infected hepatocytes and imply that indirect effects of host-viral interactions dictate viral dominance in HBV/HCV co-infected individuals.

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    • "We also built an efficient system for envelope protein expression in trans. Previous work has shown that adenoviral systems can efficiently express proteins in hepatoma cell lines (Huh-7 cells, in particular) (Dimitrova et al., 2003; Eyre et al., 2009). Hence, cDNA encoding the 21 carboxy-terminal residues of core, E1 and E2 from the JFH1 strain was used to generate adenovirus constructs expressing genotype 2a E1E2 (Ad-E1E2-2a). "
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    ABSTRACT: A trans-packaging system for hepatitis C virus (HCV) replicons lacking envelope glycoproteins was developed. The replicons were efficiently encapsidated into infectious particles after expression in trans of homologous HCV envelope proteins under the control of an adenoviral vector. Interestingly, expression in trans of core or core, p7 and NS2 with envelope proteins did not enhance trans-encapsidation. Expression of heterologous envelope proteins, in the presence or absence of heterologous core, p7 and NS2, did not rescue single-round infectious particle production. To increase the titre of homologous, single-round infectious particles in our system, successive cycles of trans-encapsidation and infection were performed. Four cycles resulted in a hundred-fold increase in the yield of particles. Sequence analysis revealed a total of 16 potential adaptive mutations in two independent experiments. Except for a core mutation in one experiment, all the mutations were located in non-structural regions mainly in NS5A (four in domain III and two near the junction with the NS5B gene). Reverse genetics studies suggested that D2437A and S2443T adaptive mutations, which are located into the NS5A-B cleavage site did not affect viral replication but enhanced the single-round infectious particles assembly only in trans-encapsidation model. In conclusion, our trans-encapsidation system enables the production of HCV single-round infectious particles. This system is adaptable and can positively select variants. The adapted variants promote trans-encapsidation and should constitute a valuable tool in the development of replicon-based HCV vaccines.
    Journal of General Virology 01/2013; 94(Pt_5). DOI:10.1099/vir.0.049676-0 · 3.18 Impact Factor
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    • "If we start HBV replication by transfection, it is more susceptible to any inhibitory influence. The work of Eyre et al explored Ad-mediated HBV replication that may be more robust than transfection [51]. "
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    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.
    PLoS ONE 09/2012; 7(9):e45146. DOI:10.1371/journal.pone.0045146 · 3.23 Impact Factor
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    • "Clinical course of HBV–HCV co-infection Viral interference between HBV and HCV operate at multiple levels, including immune responses [83]. Current evidence suggests that viral dominance of one virus over the other does not result from interactions within hepatocytes [84] [85]. From a clinical perspective, HCV–HBV co-infection can occur in different scenarios. "
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    ABSTRACT: Co-infection with either HIV or HBV in chronic hepatitis C patients is common, since all these viruses share transmission routes and geographical distribution. Interaction between these viruses generally amplifies liver damage, increasing the risk of developing end-stage liver disease and hepatocellular carcinoma. HIV-HCV co-infection is associated with poorer response to antiviral therapy. New antivirals against HCV are eagerly awaited for this population. HBV-HCV dual infections are less common. The principles guiding indication of therapy in monoinfected patients should be followed considering which virus replicates in persons with serological markers of dual HBV-HCV infection. Although there is growing evidence supporting the use of direct acting antivirals (DAA) in dually infected patients with active HCV replication, prospective trials should be conducted to demonstrate their benefit, assessing carefully the rate and clinical consequences of HBV rebounds.
    Best practice & research. Clinical gastroenterology 08/2012; 26(4):517-30. DOI:10.1016/j.bpg.2012.09.007 · 3.48 Impact Factor
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