Characterization of variants in the promoter of EBV gene BZLF1 in normal donors, HIV-positive patients and in AIDS-related lymphomas

Maurizio Martini, Daniela Capello, Diego Serraino, Assunta Navarra, Francesco Pierconti, Tonia Cenci, Gianluca Gaidano, Luigi Maria Larocca

Research output: Contribution to journalArticle

Abstract

Objective: The aim of this study was to determine the occurrence of polymorphic variants of EBV BamHI fragment Z (BZLF1) promoter zone Zp in tumor and non-tumor-associated EBV. We characterized the Zp region in type A and type B EBV, infecting AIDS-related non-Hodgkin's lymphomas (AIDS-NHL) and non-malignant lymphoid tissues derived from HIV-positive patients and from healthy individuals. Methods: The Zp region was directly sequenced in 133 EBV-positive DNA samples: 63 AIDS-NHL (32 systemic AIDS-NHL and 31 AIDS-primary central nervous system lymphoma [AIDS-PCNSL]), 30 lymphoid tissues derived from HIV-positive individuals and 40 lymphoid samples derived from healthy individuals. The chi square test was used to assess for statistically significant differences among proportions, and a two-tailed P value ≤0.05 was chosen as statistically significant. Results: We found three polymorphic Zp variants: Zp-P, considered to be the prototype sequence; Zp-V3, that differs from Zp-P for three nucleotide substitutions; and a new variant, Zp-PV, that differs from Zp-P for a single nucleotide substitution. Zp-V3 was significantly associated with AIDS-PCNSL (P <0.001) and with systemic AIDS-NHL (P = 0.007), in particular with AIDS-related immunoblastic lymphoma (P <0.001). Moreover, in malignant samples, this variant was also significantly associated with type B EBV (P <0.001). Finally, the new identified Zp-PV variant was isolated in 7 AIDS-PCNSL. Conclusions: The frequency of polymorphisms in the regulatory zone of BZLF1 is different between malignant and non-malignant samples in AIDS patients and may identify EBV subtypes with different transforming activities, including those associated to the pathogenesis of B cell lymphoma.

Original languageEnglish
Pages (from-to)298-306
Number of pages9
JournalJournal of Infection
Volume54
Issue number3
DOIs
Publication statusPublished - Mar 2007

Keywords

  • AIDS
  • Epstein-Barr virus, Non-Hodgkin's lymphoma
  • Primary central nervous system lymphoma

ASJC Scopus subject areas

  • Applied Microbiology and Biotechnology
  • Microbiology
  • Parasitology
  • Virology
  • Immunology and Allergy
  • Infectious Diseases

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