Molecular Profile of Epstein-Barr Virus in Human Immunodeficiency Virus Type 1–Related Lymphadenopathies and Lymphomas

Abstract

Human immunodeficiency virus type 1 (HIV-1)–infected patients develop a spectrum of lymphoproliferative disorders ranging from nonneoplastic lymphadenopathies to B-cell lymphomas. Although evidence suggests that Epstein-Barr virus (EBV) might be involved, its molecular profile and expression pattern in HIV-1–related lymphoproliferations remain to be defined. Using polymerase chain reaction–based techniques, we studied EBV types and variants in 28 lymphadenopathy lesions and in 20 lymphomas (15 large cell and 5 Burkitt-like). EBV was detected in 89% of lymphadenopathies and in 80% of lymphomas; viral DNA content was significantly higher in the latter. EBNA2 and LMP1 gene analysis indicated that half of the EBV+ lymphadenopathies were coinfected with both EBV type 1 and 2 strains and/or multiple type 1 variants. Conversely, all but one lymphoma carried a single viral variant, consistently type 1 in large cell lymphomas, and type 2 in Burkitt-like tumors. Most lymphomas, but no lymphadenopathies, showed monoclonal Ig heavy-chain rearrangement. Analysis of 5 large cell lymphomas and 9 lymphadenopathies for EBV transcripts identified LMP1 mRNA in most samples, and the EBNA2 transcript in all tumors. These findings provide evidence of a heterogeneous EBV population in lymphadenopathy lesions, strengthen the notion that lymphomas arise from clonal expansion of EBV+ cells, and suggest different roles for EBV types 1 and 2 in HIV-1–related lymphoproliferations.