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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 {triangledown}

Severin Gudima,1 Yiping He,1,{dagger} Ning Chai,1 Volker Bruss,2 Stephan Urban,3 William Mason,1 and John Taylor1*

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.


* Corresponding author. Mailing address: Fox Chase Cancer Center, 333 Cottman Avenue, Philadelphia, PA 19111-2497. Phone: (215) 728 2436. Fax: (215) 728-3105. E-mail: john.taylor{at}fccc.edu

{triangledown} Published ahead of print on 21 May 2008.

{dagger} Present address: USDA, Wyndmoor, PA 19038.


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.




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