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Prepublished online as a Blood First Edition Paper on September 11, 2003; DOI 10.1182/blood-2003-05-1710.

Submitted May 28, 2003
Accepted August 27, 2003
Infection of HHV-8 positive primary effusion lymphoma cells with a recombinant Epstein-Barr virus lead to restricted EBV latency, altered phenotype, and increased tumorigenicity without affecting TCL1 expression
Pankaj Trivedi*, Kumi Takazawa, Claudia Zompetta, Laura Cuomo, Elena Anastasiadou, Antonino Carbone, Stefania Uccini, Filippo Belardelli, Kenzo Takada, Luigi Frati, and Alberto Faggioni
Department of Experimental Medicine and Pathology, Istituto Pasteur-Fondazione Cenci Bolognetti, University of Rome, Rome, Italy
Department of Tumor Virology, Institute for Genetic Medicine, Hokkaido University, Sapporo, Japan
Department of Clinical Pathology, San Filippo Neri Hospital, Rome, Italy
Department of Pathology and Scientific Direction, Centro di Riferimento Oncologico, National Cancer Institute, Aviano, Italy
Laboratory of Virology, Istituto Superiore di Sanita, Rome, Italy
Neuromed, INM, Pozzilli, Italy
* Corresponding author; email: pankaj.trivedi{at}uniroma1.it.
To investigate the role of EBV in the pathogenesis of PEL, we infected HHV-8 positive (HHV-8pos) but EBV negative (EBVneg) PEL lines BC-3, CRO-AP/6 and CRO-AP/3 cells with the recombinant Akata EBV strain. All EBV infected clones expressed EBER-1, EBNA-1 and LMP2A. The expression of LMP1 and LMP2B was variable. None however expressed EBNA2-6. The surface markers CD30, CD74 and Syndecan-1 were downregulated in EBV convertants. EBV infected BC-3 and CRO-AP/6 cells were highly tumorigenic in SCID mice in contrast to their respective EBV negative parental cells. However, neither the parental cells nor the virus converted counterparts expressed TCL1. The results showing that PELs upon in vitro EBV infection do not sustain latency III in spite of the absence of immune pressure indicate that the choice of EBV latent gene expression program is cell dependent. The data suggest an important role of EBV in the pathogenesis of PEL.

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