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Journal of Virology, October 1998, p. 8143-8149, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.

Persistent Infection of Epstein-Barr Virus-Positive B Lymphocytes by Human Herpesvirus 8

Stefanie Kliche,1 Elisabeth Kremmer,2 Wolfgang Hammerschmidt,3 Ulrich Koszinowski,1 and Jürgen Haas1,*

Max-von-Pettenkofer Institut, Genzentrum, Universität München, 81377 Munich,1 and Institut für Immunologie2 and Institut für Klinische Molekularbiologie und Tumorgenetik,3 GSF Forschungszentrum, 80377 Munich, Germany

Received 17 April 1998/Accepted 2 July 1998

In patients with Kaposi's sarcoma (KS), human herpesvirus 8 (HHV-8) can invariably be detected in KS tumor tissue and, at a lower frequency, in prostate tissue and peripheral blood B lymphocytes. Whereas the majority of KS spindle cells are latently infected by HHV-8, linear HHV-8 genomes characteristic for lytic infection are found predominantly in the peripheral blood cells of KS patients. In this study, we show that HHV-8 can stably infect B lymphocytes in vitro in the presence of Epstein-Barr virus (EBV). We were able to generate immortalized HHV-8+/EBV+ lymphoblastoid cell lines (LCLs) derived from peripheral blood mononuclear cells (PBMC) of EBV- and EBV+ donors. In HHV-8+/EBV+ LCLs, which have the phenotype of activated B lymphocytes (CD19+, surface immunoglobulin M, CD23+, CD30+, CD80+), HHV-8 was still present after more than 25 passages (more than 9 months of culture). Latent viral transcripts and proteins were present in nonstimulated HHV-8+/EBV+ LCLs. After induction by phorbol ester and n-butyrate, HHV-8+/EBV+ LCLs expressed lytic HHV-8 transcripts and proteins. Moreover, HHV-8 could be serially passaged from HHV-8+/EBV+ LCLs to fresh PBMC.

* Corresponding author. Mailing address: Max-von-Pettenkofer Institut, Genzentrum, Universität München, Feodor-Lynen-Str. 25, 81377 Munich, Germany. Phone: 49 89 74017 201. Fax: 49 89 74017 250. E-mail: haas{at}lmb.uni-muenchen.de.

Journal of Virology, October 1998, p. 8143-8149, Vol. 72, No. 10
0022-538X/98/$04.00+0
Copyright © 1998, American Society for Microbiology. All rights reserved.


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