Publications (3)12.62 Total impact
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Article: Enzymatic treatment of duck hepatitis B virus: topology of the surface proteins for virions and noninfectious subviral particles.
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ABSTRACT: The large surface antigen L of duck hepatitis B virus exhibits a mixed topology with the preS domains of the protein alternatively exposed to the particles' interior or exterior. After separating virions from subviral particles (SVPs), we compared their L topologies and showed that both particle types exhibit the same amount of L with the following differences: 1--preS of intact virions was enzymatically digested with chymotrypsin, whereas in SVPs only half of preS was accessible, 2--phosphorylation of L at S118 was completely removed by phosphatase treatment only in virions, 3--iodine-125 labeling disclosed a higher ratio of exposed preS to S domains in virions compared to SVPs. These data point towards different surface architectures of virions and SVPs. Because the preS domain acts in binding to a cellular receptor of hepatocytes, our findings implicate the exclusion of SVPs as competitors for the receptor binding and entry of virions.Virology 04/2007; 359(1):126-36. · 3.35 Impact Factor -
Article: Chronic infection with hepatitis B viruses and antiviral drug evaluation in uPA mice after liver repopulation with tupaia hepatocytes.
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ABSTRACT: Transplantation of primary human hepatocytes and establishment of hepatitis B virus (HBV) infection in immunodeficient urokinase plasminogen activator (uPA) transgenic mice was shown. However, the availability of usable primary human hepatocytes is very limited. Therefore, alternative and more accessible sources of hepatocytes permissive for HBV infection are highly desirable. Here we investigated the potential of primary hepatocytes from the tree shrew Tupaia belangeri that were shown to be susceptible to HBV infection. Freshly isolated or cryopreserved primary tupaia hepatocytes were transplantated via intrasplenic injection into immunodeficient uPA/RAG-2 mice. Engrafted mice were then infected with HBV and woolly monkey (WM)-HBV positive sera. Extensive proliferation of xenografted cells was demonstrated by the stable production of tupaia alpha1-antitrypsin in serum and liver of transplanted mice. Quantitative PCR assays demonstrated the presence of circulating viral particles as well as intracellular viral DNA, including covalently closed circular (ccc) DNA, in transplanted mice. Viral infection could be serially passaged in mice. Furthermore, viral replication was strongly inhibited by treating mice with adefovir dipivoxil. uPA mice repopulated with tupaia hepatocytes represent a useful and more accessible model for HBV infection studies, including the evaluation of antiviral therapy and cccDNA.Journal of Hepatology 02/2005; 42(1):54-60. · 9.26 Impact Factor -
Article: Modulation of the Nuclear Transcription Factor of Activated T Cells by Duck Hepatitis B Virus
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ABSTRACT: During infection with hepadnaviruses besides the infectious agent a high number of subviral particles without nucleocapsids are produced, which are able to change the infection dramatically. In addition, it was observed that the activation of the nuclear factor of activated T cells, regulated usually in cells of the immune system, was strongly influenced after infection. When primary duck liver cells were infected with purified virions of duck hepatitis B virus the activation of this factor was reduced in a similar way as it was achieved by inhibition of calcineurin, a cellular phosphatase necessary to control the factor, whereas the addition of subviral particles inhibited this reduction. It was found that the large surface protein of the virus was responsible for the reduced activity. Although this protein was embedded in similar amounts into the envelopes of both particles, only virions were able to inhibit the activity of the nuclear factor. An explanation of the different performances of the particles in primary duck liver cells apparently depends on the individual mode of insertion of the large surface proteins into the viral membrane. Furthermore, the nuclear factor of activated T cells could only be detected in liver sinusoidal endothelial cells, which was shown being attracted by virions but not by subviral particles.Nature Precedings.
