Epstein-Barr virus (EBV) replicative gene expression in tumour cells of AIDS-related non-Hodgkin's lymphoma in relation to CD4 cell number and antibody titres to EBV.
OBJECTIVE
To determine whether activation of Epstein-Barr virus (EBV) replication in tumour cells of AIDS-related non-Hodgkin's lymphoma (ARNHL) is correlated with CD4+ cell counts and influences antibody response to EBV [anti-Z Epstein-Barr replicative activator (ZEBRA), anti-early antigen (EA), anti-viral capsid antigen (VCA)].


METHODS
Retrospective study based on immunohistochemistry and in situ hybridization to detect EBV replicative gene products in tissue samples from patients affected by ARNHL and correlation with CD4+ cell counts and results of EBV serology (including anti-ZEBRA activity) in sera from the same patients.


METHODS
Seventeen out of 22 cases of ARNHL were selected for the presence of EBV [Epstein-Barr early region (EBER) RNA-positive]. Immunohistochemistry was performed with anti-ZEBRA, anti-EA-restricted, anti-VCA antibodies and in situ hybridization with BHLF1/NotI oligoprobes on tumour samples. Results were statistically correlated with those of CD4+ cell counts (17 out of 17) and with anti-EBV antibody titres (13 out of 17) assessed using standard immunofluorescence method and enzyme-linked immunosorbent assay procedure using recombinant ZEBRA protein and synthetic peptides as antigens.


RESULTS
BZLF1 (ZEBRA) or early gene products (EA-R and EA-D/BHLF1/NotI) were detected in a small proportion (< 0.01-5%) of tumour cells in eight of these 17 cases by immunohistochemistry and in situ hybridization. Demonstration of replicative gene expression did not correlate with either low CD4+ cell counts (P > 0.05) or anti-EBV antibody titres (P > 0.05). Anti-ZEBRA activity was not significantly increased in patients affected with ARNHL, the cells of which expressed replicative gene products (P > 0.05).


CONCLUSIONS
The degree of immunodeficiency does not clearly enhance replicative gene expression in tumour cells of ARNHL. EBV serology, including anti-ZEBRA activity, is not a reliable tool for predicting the occurrence of such proliferations.
Brousset
P
P
Department of Pathology, Centre Hospitalier Universitaire de Purpan, Toulouse, France.
Drouet
E
E
Schlaifer
D
D
Icart
J
J
Payen
C
C
Meggetto
F
F
Marchou
B
B
Massip
P
P
Delsol
G
G
D000163:Acquired Immunodeficiency Syndrome / Q000150:complications; D000328:Adult; D000914:Antibodies, Viral / Q000096:biosynthesis / Q000097:blood*; D000918:Antibody Specificity; D000956:Antigens, Viral / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes; D036022:Capsid Proteins; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D004797:Enzyme-Linked Immunosorbent Assay; D019309:Epstein-Barr Virus Nuclear Antigens; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D006566:Herpesviridae Infections / Q000150:complications; D004854:Herpesvirus 4, Human / Q000235:genetics* / Q000276:immunology / Q000502:physiology; D006801:Humans; D007958:Leukocyte Count; D016483:Lymphoma, AIDS-Related / Q000382:microbiology*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D014412:Tumor Virus Infections / Q000150:complications; D014764:Viral Proteins; D014775:Virus Activation; D014779:Virus Replication
D000914:Antibodies, Viral; D000956:Antigens, Viral; C063676:BZLF1 protein, Herpesvirus 4, Human; D036022:Capsid Proteins; D004268:DNA-Binding Proteins; D019309:Epstein-Barr Virus Nuclear Antigens; C041788:Epstein-Barr viral capsid antigen; C033305:Epstein-Barr virus early antigen; D015534:Trans-Activators; D014764:Viral Proteins