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Journal of Virology, September 2003, p. 9511-9521, Vol. 77, No. 17
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.17.9511-9521.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.

Pre-S1 Antigen-Dependent Infection of Tupaia Hepatocyte Cultures with Human Hepatitis B Virus

Dieter Glebe,1* Mehriar Aliakbari,1 Peter Krass,1 Eva V. Knoop,1 Klaus P. Valerius,2 and Wolfram H. Gerlich1

Institute of Medical Virology,1 Institute of Anatomy and Cell Biology, Justus Liebig University Giessen, 35392 Giessen, Germany2

Received 13 February 2003/ Accepted 3 June 2003

The susceptibility of the tree shrew Tupaia belangeri to human hepatitis B virus (HBV) has been demonstrated both in vivo and in vitro. In this study, we show that purified HBV infects primary T. belangeri hepatocyte cultures in a very specific manner, as detected by HBV covalently closed circular DNA, mRNA, HBV e antigen, and HBsAg production. A monoclonal antibody (MAb), MA18/7, directed against the pre-S1 domain of the large HBs protein, which has been shown to neutralize infectivity of HBV for primary human hepatocytes, also blocked infection of primary Tupaia hepatocytes. MAbs against the pre-S2 domain of HBs inhibited infection only partially, whereas an S MAb and polyvalent anti-HBs antibodies neutralized infection completely. Thus, both pre-S1 and S antigens are necessary for infection in the tupaia. Using subviral particles, >70% of primary Tupaia hepatocytes are capable of specific binding of pre-S1-rich HBsAg, showing localization in distinct membrane areas. The data show that the early steps of HBV infection in Tupaia hepatocyte cultures are comparable to those in the human system.

* Corresponding author. Mailing address: Institute of Medical Virology, Justus Liebig University Giessen, Frankfurter Strasse 107, 35392 Giessen, Germany. Phone: 49 641 9941203. Fax: 49 641 99 41209. E-mail: dieter.glebe{at}viro.med.uni-giessen.de.

Journal of Virology, September 2003, p. 9511-9521, Vol. 77, No. 17
0022-538X/03/$08.00+0     DOI: 10.1128/JVI.77.17.9511-9521.2003
Copyright © 2003, American Society for Microbiology. All Rights Reserved.



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