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Journal of Virology, August 2008, p. 7276-7283, Vol. 82, No. 15
0022-538X/08/$08.00+0     doi:10.1128/JVI.00576-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

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

Severin Gudima,¹ Yiping He,^1, Ning Chai,¹ Volker Bruss,² Stephan Urban,³ William Mason,¹ and John Taylor^1*

Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, Pennsylvania 19111,¹ Department of Virology, University of Goettingen, Goettingen 37075, Germany,² Department for Molecular Virology, University of Heidelberg, Heidelberg 69120, Germany³

Received 14 March 2008/ Accepted 12 May 2008

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.

Published ahead of print on 21 May 2008.

Present address: USDA, Wyndmoor, PA 19038.