Latent membrane protein 1 deletion mutants accumulate in reed-sternberg cells of human immunodeficiency virus-related Hodgkin's lymphoma.
The origin and biological significance of deletions at the 3' end of the Epstein-Barr virus (EBV)-encoded latent membrane protein 1 (LMP-1) gene are still controversial. We herein demonstrate that LMP-1 deletion mutants are highly associated with human immunodeficiency virus-related Hodgkin's lymphoma (HIV-HL) of Italian patients (29 of 31 cases; 93.5%), a phenomenon that is not due to a peculiar distribution of EBV strains in this area. In fact, although HIV-HL patients are infected by multiple EBV variants, we demonstrate that LMP-1 deletion mutants preferentially accumulate within neoplastic tissues. Subcloning and sequencing of the 3' LMP-1 ends of two HIV-HL genes in which both variants were present showed the presence of molecular signatures suggestive of a likely derivation of the LMP-1 deletion mutant from a nondeletion ancestor. This phenomenon likely occurs within tumor cells in vivo, as shown by the detection of both LMP-1 variants in single microdissected Reed-Sternberg cells, and may at least in part explain the high prevalence of LMP-1 deletions associated with HIV-HL.
Guidoboni
Massimo
M
Immunovirology and Biotherapy Unit, Department of Pre-Clinical and Epidemiological Research, Centro di Riferimento Oncologico, IRCCS, National Cancer Institute, via Pedemontana Occidentale 12, 33081 Aviano (PN) Italy.
Ponzoni
Maurilio
M
Caggiari
Laura
L
Lettini
Antonia A
AA
Vago
Luca
L
De Re
Valli
V
Gloghini
Annunziata
A
Zancai
Paola
P
Carbone
Antonino
A
Boiocchi
Mauro
M
Dolcetti
Riccardo
R
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D003598:Cytoskeletal Proteins; D017353:Gene Deletion; D006566:Herpesviridae Infections / Q000453:epidemiology / Q000821:virology*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification*; D006689:Hodgkin Disease / Q000235:genetics / Q000378:metabolism* / Q000821:virology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D016483:Lymphoma, AIDS-Related / Q000473:pathology*; D016539:Reed-Sternberg Cells / Q000378:metabolism* / Q000821:virology
D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; C484380:PDLIM7 protein, human