Infection of HHV-8+ primary effusion lymphoma cells with a recombinant Epstein-Barr virus leads to restricted EBV latency, altered phenotype, and increased tumorigenicity without affecting TCL1 expression.
To investigate the role of Epstein-Barr virus (EBV) in the pathogenesis of primary effusion lymphoma (PEL), we infected human herpesvirus 8 (HHV-8+) but EBV- 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 down-regulated in EBV convertants. EBV-infected BC-3 and CRO-AP/6 cells were highly tumorigenic in severe combined immunodeficiency (SCID) mice in contrast to their respective EBV- parental cells. However, neither the parental cells nor the virus-converted counterparts expressed TCL1. The results showing that PEL cells on in vitro EBV infection do not sustain latency III despite 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.
Trivedi
Pankaj
P
Department of Experimental Medicine and Pathology, University of Rome, "La Sapienza," Rome, Italy. pankaj.trivedi@uniroma1.it
Takazawa
Kumi
K
Zompetta
Claudia
C
Cuomo
Laura
L
Anastasiadou
Elena
E
Carbone
Antonino
A
Uccini
Stefania
S
Belardelli
Filippo
F
Takada
Kenzo
K
Frati
Luigi
L
Faggioni
Alberto
A
D000818:Animals; D045744:Cell Line, Tumor; D020031:Epstein-Barr Virus Infections / Q000473:pathology / Q000821:virology*; D015870:Gene Expression; D006566:Herpesviridae Infections / Q000235:genetics / Q000821:virology*; D019288:Herpesvirus 8, Human / Q000472:pathogenicity*; D006801:Humans; D008223:Lymphoma / Q000473:pathology / Q000821:virology*; D051379:Mice; D016513:Mice, SCID; D009368:Neoplasm Transplantation; D011518:Proto-Oncogene Proteins / Q000235:genetics; D011995:Recombination, Genetic; D014183:Transplantation, Heterologous
D011518:Proto-Oncogene Proteins; C090851:TCL1A protein, human; C490393:Tcl1 protein, mouse