Hepatitis B virus and hepatitis C virus interaction in Huh-7 cells
ABSTRACT 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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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; DOI:10.1099/vir.0.049676-0 · 3.53 Impact Factor
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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 · 3.28 Impact Factor
- Viral Hepatitis - Selected Issues of Pathogenesis and Diagnostics, 11/2011; , ISBN: 978-953-307-760-4