Primary Human Hepatocytes Are Susceptible to Infection by Hepatitis Delta Virus Assembled with Envelope Proteins of Woodchuck Hepatitis Virus

Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111-2497, USA.
Journal of Virology (Impact Factor: 4.44). 09/2008; 82(15):7276-83. DOI: 10.1128/JVI.00576-08
Source: PubMed


Hepatitis B virus (HBV) and hepatitis delta virus (HDV) share the HBV envelope proteins. When woodchucks chronically infected
with woodchuck hepatitis virus (WHV) are superinfected with HDV, they produce HDV with a WHV envelope, wHDV. Several lines
of evidence are provided that wHDV infects not only cultured primary woodchuck hepatocytes (PWH) but also primary human hepatocytes
(PHH). Surprisingly, HBV-enveloped HDV (hHDV) and wHDV infected PHH with comparable efficiencies; however, hHDV did not infect
PWH. The basis for these host range specificities was investigated using as inhibitors peptides bearing species-specific pre-S
(where S is the small envelope protein) sequences. It was found that pre-S1 contributed to the ability of wHDV to infect both
PHH and PWH. In addition, the inability of hHDV to infect PWH was not overcome using a chimeric form of hHDV containing WHV
S protein, again supporting the essential role of pre-S1 in infection of target cells. One interpretation of these data is
that host range specificity of HDV is determined entirely by pre-S1 and that the WHV and HBV pre-S1 proteins recognize different
receptors on PHH.

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Available from: Stephan Urban, Mar 10, 2014
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    • "Recent data, however, raise the question whether HDV is a suitable model system to study HBV entry. While chimeric particles harboring woodchuck envelope proteins are unable to infect PHHs, a recombinant HDV assembled with envelope proteins of WHV infects PHHs, indicating significant differences between the entry process of HDV and HBV [113]. Detailed analysis of the TLM-mutated HBV [112] reveals that due to the partial deletion of either the C-terminal or N-terminal part of the TLM a novel functional TLM was generated. "
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    • "The HBsAg coat is not exclusive, as HDV can coat also within the woodchuck hepatitis virus (WHV) surface antigen and in vivo HDV has been passed from chimpanzees to the rodent [4]. However, in apparent contradiction to the in vivo transmission of primate HDV to woodchucks, woodchuck-HDV was reported to infect cultured primary woodchuck hepatocytes as well as cultures of primary human hepatocytes, but human HDV could not infect woodchuck hepatocytes [22]; the different host-range specificities seems determined by the different recognition of WHV and HBV Pre S1 proteins on human hepatocytes. Conventional RNA viruses undergo replication by a virus encoded RNA-dependent RNA-polymerase which replicates the viral genome; they cannot use cellular RNA-polymerases, as these accept only DNA templates . "
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