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1996-02-26
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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).