Characterization of Epstein-Barr virus genotype in AIDS-related non-Hodgkin's lymphoma.
In the present study sequence variations at the C terminus of the Epstein-Barr virus (EBV) nuclear antigen 1 (EBNA-1), EBV-encoded latent membrane protein 1 (LMP-1), and EBNA-2 and EBNA-3C genes were investigated in 64 cases of EBV-positive AIDS-related diffuse large cell lymphoma (AIDS-DLCL), both systemic (12) and localized primarily to the central nervous system (52), and in 12 cases of EBV-positive AIDS-related Burkitt's lymphoma (AIDS-BL). Sequence analysis of the EBNA-1 C-terminal region led to the distinction of two major unrelated EBV strains, termed strain P (prototype) and strain V (variant), and their related subtypes, namely P-ala, P-thr, V-leu, V-val, and V-pro. Analysis of the LMP-1 gene was performed to assess the frequency of the C-terminus deletion variant, whereas analysis of EBNA-2 and EBNA-3C genes led to the identification of the distribution of the EBV type 1 and type 2 strains. The frequency of EBNA-1 subtypes was assessed in 49 cases of AIDS-NHL, including 37 cases of AIDS-DLCL and 12 cases of AIDS-BL. The P strain was detected in 45 of 49 cases (91.8%) whereas the V strain was found in 4 of 49 samples (8.1%). A significant difference in the distribution of the P and V strains was found between AIDS-DLCL and AIDS-BL (p < 0.01), because of the exclusive infection by the P strain of the AIDS-DLCL samples analyzed. The frequency of LMP-1 deletion variants and of EBV type 1 and type 2 strains in AIDS-DLCL overlapped with that of the general population, and no correlation was found with the evaluated clinicoepidemiological data of patients, that is, disease site, tumor histology, CD4(+) cell counts, and HIV transmission route. In conclusion, we found that the distribution of the EBV genotype in all of the AIDS-NHL samples analyzed is similar to the viral representation found in control individuals of both immunocompetent and immunocompromised populations.
Fassone
Lucia
L
Division of Internal Medicine, Department of Medical Sciences, Amedeo Avogadro University of Eastern Piedmont, Novara, Italy.
Cingolani
Antonella
A
Martini
Maurizio
M
Migliaretti
Giuseppe
G
Oreste
Pier Luigi
PL
Capello
Daniela
D
Gloghini
Annunziata
A
Vivenza
Daniela
D
Dolcetti
Riccardo
R
Carbone
Antonino
A
Antinori
Andrea
A
Gaidano
Gianluca
G
Larocca
Luigi Maria
LM
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000956:Antigens, Viral / Q000235:genetics; D002051:Burkitt Lymphoma / Q000453:epidemiology / Q000276:immunology / Q000821:virology; D018791:CD4 Lymphocyte Count; D002352:Carrier Proteins / Q000235:genetics; D003598:Cytoskeletal Proteins; D019309:Epstein-Barr Virus Nuclear Antigens / Q000235:genetics; D017353:Gene Deletion; D005838:Genotype; D004854:Herpesvirus 4, Human / Q000737:chemistry / Q000235:genetics*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; D016483:Lymphoma, AIDS-Related / Q000453:epidemiology / Q000276:immunology / Q000821:virology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000453:epidemiology / Q000276:immunology / Q000821:virology; D008228:Lymphoma, Non-Hodgkin / Q000453:epidemiology / Q000276:immunology / Q000821:virology*; D008969:Molecular Sequence Data; D012307:Risk Factors; D016415:Sequence Alignment; D014764:Viral Proteins; D016335:Zinc Fingers / Q000235:genetics
D048868:Adaptor Proteins, Signal Transducing; D000956:Antigens, Viral; D002352:Carrier Proteins; D003598:Cytoskeletal Proteins; C402641:EBNA-2 protein, Human herpesvirus 4; C498774:EBNA-3C, epstein-barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; C484380:PDLIM7 protein, human; D014764:Viral Proteins; C417029:EBV-encoded nuclear antigen 1