Mono/oligoclonal pattern of Kaposi Sarcoma-associated herpesvirus (KSHV/HHV-8) episomes in primary effusion lymphoma cells.
Primary effusion lymphoma (PEL) is a rare lymphoma of B-cell origin, developed in serous cavities. PEL tumor cells are latently infected with Kaposi sarcoma-associated herpesvirus (KSHV) and in most cases co-infected with Epstein-Barr virus (EBV). In 15 primary PEL tumors including 10 EBV-positive cases, we analyzed the fused terminal repeat (TR) regions of KSHV episomes using pulsed-field gel electrophoresis and Southern blot. On the same genomic DNA samples, the cellular clonality was assessed by Southern blot and PCR detection of monoclonal immunoglobulin heavy chain (IGH) VDJ gene rearrangements, associated in the EBV-infected cases, with Southern blot analysis of the fused termini of EBV episomes. Monoclonal IGH gene rearrangements were detected in 13 tumors using Southern blot, in 11 cases using PCR, and in all cases considering both methods. EBV infection was monoclonal in all EBV-positive cases. However, only 5 PEL tumors were found to be monoclonally infected with KSHV. In the 10 other cases, we found a biclonal (2 bands; n = 4) or an oligoclonal pattern (3-6 bands; n = 6) of KSHV episomes. We hypothesized that the apparent discrepancy between viral and cellular clonalities in PEL might be due to several phenomena including complex mechanisms of genomic recircularization, insertion of duplicated sequences into the TR region and simultaneous infection of tumor cells with defective KSHV variants. KSHV infection of contaminating nontumoral cells, superinfection from lytically infected cells or viral integration events might also explain the oligoclonal pattern of KSHV infection. Several of these mechanisms, not mutually exclusive, might coexist in a single tumor.
Boulanger
Emmanuelle
E
Unité d'Epidémiologie et de Physiopathologie des Virus Oncogènes, Institut Pasteur, Paris, France. emmaboul@pasteur.fr
Duprez
Renan
R
Delabesse
Eric
E
Gabarre
Jean
J
Macintyre
Elizabeth
E
Gessain
Antoine
A
D000328:Adult; D000368:Aged; D015703:Antigens, CD / Q000097:blood; D016521:Electrophoresis, Gel, Pulsed-Field; D005260:Female; D019288:Herpesvirus 8, Human / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D016393:Lymphoma, B-Cell / Q000276:immunology / Q000821:virology*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D015183:Restriction Mapping; D012514:Sarcoma, Kaposi / Q000276:immunology / Q000821:virology*
D015703:Antigens, CD; D007143:Immunoglobulin Heavy Chains