Heterogeneous expression of Epstein-Barr virus latent proteins in endemic Burkitt's lymphoma.
Epstein-Barr virus (EBV)-infected cells may sustain three distinct forms of virus latency. In lymphoblastoid cell lines, six EBV-encoded nuclear antigens (EBNA1, 2, 3A, 3B, 3C, -LP), three latent membrane proteins (LMP1, 2A, 2B), and two nuclear RNAs (EBERs) are expressed. This form of latency, termed latency III, is also encountered in some posttransplant lymphoproliferative disorders. In EBV-positive cases of Hodgkin's disease, the EBERs, EBNA1, and the LMPs are expressed (latency II), whereas in Burkitt's lymphoma (BL) only the EBERs and EBNA1 have been detected (latency I). We have studied the expression of EBV proteins in 17 cases of EBV-positive endemic BL by immunohistology. Expression of LMP1 was seen in variable proportions of tumor cells in two cases and EBNA2 was detected in some tumor cells in three other cases. Also, the BZLF1 trans-activator protein was expressed in a few tumor cells in 6 cases, indicating entry into the lytic cycle. A phenotypic drift from latency I to latency III has been observed previously in some BL cell lines. Our results suggest that a similar phenomenon may occur in BL in vivo and indicate that the operational definition of EBV latencies is not easily applied to human tumors.
Niedobitek
G
G
Department of Pathology, University of Birmingham, UK.
Agathanggelou
A
A
Rowe
M
M
Jones
E L
EL
Jones
D B
DB
Turyaguma
P
P
Oryema
J
J
Wright
D H
DH
Young
L S
LS
D000293:Adolescent; D000956:Antigens, Viral / Q000096:biosynthesis / Q000235:genetics; D001402:B-Lymphocytes / Q000378:metabolism* / Q000821:virology; D002051:Burkitt Lymphoma / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D002471:Cell Transformation, Neoplastic; D002472:Cell Transformation, Viral; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D019309:Epstein-Barr Virus Nuclear Antigens; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015967:Gene Expression Regulation, Viral; D006566:Herpesviridae Infections / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D017730:Ki-1 Antigen / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000821:virology; D010641:Phenotype; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis / Q000235:genetics; D019253:Proto-Oncogene Proteins c-bcl-2; D012367:RNA, Viral / Q000096:biosynthesis* / Q000235:genetics; D015534:Trans-Activators / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured; D014412:Tumor Virus Infections / Q000378:metabolism* / Q000473:pathology / Q000821:virology; D014763:Viral Matrix Proteins / Q000096:biosynthesis / Q000235:genetics; D014764:Viral Proteins / Q000096:biosynthesis* / Q000235:genetics; D017735:Virus Latency; D014779:Virus Replication
D000956:Antigens, Viral; C063676:BZLF1 protein, Herpesvirus 4, Human; D004268:DNA-Binding Proteins; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D019309:Epstein-Barr Virus Nuclear Antigens; D017730:Ki-1 Antigen; D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012367:RNA, Viral; D015534:Trans-Activators; D014763:Viral Matrix Proteins; D014764:Viral Proteins