       Document 0588
 DOCN  M9620588
 TI    Characteristics of EBV-infected cells in HIV-related lymphadenopathy:
       implications for the pathogenesis of EBV-associated and EBV-unrelated
       lymphomas of HIV-seropositive individuals.
 DT    9602
 AU    Dolcetti R; Gloghini A; De Vita S; Vaccher E; De Re V; Tirelli U;
       Carbone A; Boiocchi M; Division of Experimental Oncology 1, INRCCS,
       Aviano (PN), Italy.
 SO    Int J Cancer. 1995 Nov 27;63(5):652-9. Unique Identifier : AIDSLINE
       MED/96083713
 AB    The present study was performed with the aim of better defining the
       possible role of Epstein-Barr-virus (EBV)-infected cells in the
       pathogenesis of HIV-related lymphadenopathy syndrome (LAS). In addition,
       since LAS has been considered as a pre-lymphomatous lesion, we also
       wished to elucidate the possible contribution of EBV-carrying cells
       present in LAS tissues to the development of HIV-associated malignant
       lymphomas. To this end, we have characterized EBV-infected cells in LAS
       lymph nodes in terms of EBV DNA prevalence, tissue distribution in
       relation to HIV-carrying cells, virus sub-type, expression of latent and
       replicative antigens, and presence of clonal EBV episomes. When compared
       with HIV-unrelated lymphadenopathies (4/10, 40%), LAS showed a higher
       prevalence of EBV DNA (14/20, 70%). Comparable values of EBV prevalence
       were detected in LAS with follicular hyperplasia (12/16, 75%) and with
       follicular involution (4/4, 100%). All EBV+ non-neoplastic lymph nodes
       from HIV-seronegative patients carried type-I EBV, whereas LAS specimens
       showed almost equivalent distribution of the 2 EBV sub-types. Of the 14
       EBV-carrying LAS, 4 (29%) were positive by Southern-blot analysis for
       the BamHI-W region of the virus genome but negative for the presence of
       monoclonal EBV episomes. In situ hybridization revealed a remarkably
       higher load of EBV-infected cells in LAS than in HIV-unrelated
       lymphadenopathies. In LAS lymph nodes, EBV-carrying cells were
       identified as isolated, cytologically normal elements, sometimes with
       immunoblastic morphology, usually scattered throughout the
       interfollicular areas. By contrast, the expression of HIV p24 was
       restricted to germinal center cells. All the EBV+ LAS samples were
       negative for the expression of EBV-encoded latent (LMP-1 and EBNA-2) and
       replicative proteins (BZLF-1, BHLF-1, EA-D, EA-R and VCA). In addition,
       amplification of the immunoglobulin heavy-chain genes using 2 different
       polymerase-chain-reaction protocols showed evidence of B-cell clonal
       expansion in 2/20 (10%) LAS, one EBV- case, and one sample with low
       numbers of EBV-infected cells. These results suggest that (i)
       EBV-carrying cells are probably not involved in the development of LAS,
       either directly or indirectly; (ii) type-2-EBV-infected cells are
       present in LAS lymph nodes from the early phases of HIV infection; (iii)
       EBV-carrying LAS per se probably does not constitute a lesion at high
       risk for subsequent development of EBV+ lymphomas; (iv) it is unlikely
       that a high viral load or strong EBV-mediated antigenic stimulation
       plays a contributory role in the development of EBV-unrelated lymphomas
       of HIV-seropositive individuals.
 DE    Antigens, Viral/ANALYSIS  AIDS-Related Complex/PATHOLOGY/*VIROLOGY
       B-Lymphocytes/IMMUNOLOGY  Burkitt's Lymphoma/PATHOLOGY/*VIROLOGY  DNA,
       Viral/ANALYSIS  Herpesviridae Infections/*COMPLICATIONS  *Herpesvirus 4,
       Human/GENETICS/IMMUNOLOGY  Human  HIV Core Protein p24/ANALYSIS  HIV
       Seropositivity/*VIROLOGY  Lymph Nodes/PATHOLOGY/VIROLOGY  Lymphocyte
       Transformation  Lymphoma, AIDS-Related/PATHOLOGY/*VIROLOGY  Support,
       Non-U.S. Gov't  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

