Latent membrane protein 1 deletion mutants accumulate in Reed-Sternberg cells of human immunodeficiency virus-related Hodgkin's lymphoma

Massimo Guidoboni, Maurilio Ponzoni, Laura Caggiari, Antonia A. Lettini, Luca Vago, Valli De Re, Annunziata Gloghini, Paola Zancai, Antonino Carbone, Mauro Boiocchi, Riccardo Dolcetti

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)2643-2649
Number of pages7
JournalJournal of Virology
Volume79
Issue number4
DOIs
Publication statusPublished - Feb 2005

ASJC Scopus subject areas

  • Immunology

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