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Journal of Virology, February 2005, p. 2643-2649, Vol. 79, No. 4
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.4.2643-2649.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Latent Membrane Protein 1 Deletion Mutants Accumulate in Reed-Sternberg Cells of Human Immunodeficiency Virus-Related Hodgkin's Lymphoma

Massimo Guidoboni,1 Maurilio Ponzoni,2 Laura Caggiari,1 Antonia A. Lettini,1 Luca Vago,3 Valli De Re,4 Annunziata Gloghini,5 Paola Zancai,1 Antonino Carbone,5 Mauro Boiocchi,4 and Riccardo Dolcetti1*

Immunovirology and Biotherapy Unit,1 Division of Experimental Oncology 1, Department of Pre-Clinical and Epidemiological Research,4 Division of Pathology, Centro di Riferimento Oncologico, IRCCS, National Cancer Institute, Aviano, Pordenone,5 Department of Pathology, S. Raffaele H. Scientific Institute,2 Institute of Biomedical Sciences "L. Sacco," Milan, Italy3

Received 16 March 2004/ Accepted 5 July 2004

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.

* Corresponding author. Mailing address: 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. Phone: 39 0434 659660. Fax: 39 0434 659659. E-mail: rdolcetti{at}cro.it.

Journal of Virology, February 2005, p. 2643-2649, Vol. 79, No. 4
0022-538X/05/$08.00+0     doi:10.1128/JVI.79.4.2643-2649.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.





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