Expression of Epstein–Barr virus replicative proteins in aids‐related non‐Hodgkin's lymphoma cells

Abstract

Epstein-Barr virus (EBV) infection in lymphoproliferative lesions has been assumed to be strictly latent. In order to investigate the possible occurrence of EBV replication in AIDS-related lymphoma (ARL) cells, we studied 13 cases by immunohistology using monoclonal antibodies to the EBV-encoded switch-protein BZLF1, early antigens (EAs), late replicative proteins [virus capsid antigens (VCAs) and membrane antigens (MAs)], and to the latent proteins EB nuclear antigen 2 (EBNA 2) and latent membrane protein (LMP). EBV genomes were detected by in situ hybridization. EBV genomes and/or gene products were demonstrated in ten cases, including all immunoblast-rich lymphomas, two Burkitts lymphomas, and a T-cell anaplastic large-cell lymphoma. The BZLF1 protein, which disrupts latency in B cells, was identified in six (60 per cent), and EAs in four (40 per cent) of the EBV-positive ARL. Only one lymphoma (10 per cent) expressed VCAs and MAs. EBNA 2 and LMP were detected in three (30 per cent) and eight (80 per cent) of EBV-positive cases, respectively. EBV DNA was detected in lymphoma cells in 7 of 12 (58 per cent) cases. The most important finding of this study was frequent spontaneous activation of latent EBV in ARL. Production of complete virus, however, was either aborted, or tumour cells expressing late productive cycle proteins (VCA, MA) were rapidly cleared from tissues. It is suggested that host factors that normally inhibit replication of EBV are deficient in AIDS patients.

Functional and physical interaction between p53 and BZLF1: implications for Epstein-Barr virus latency.

“…Protein extracts were harvested after 12 h of anti-IgG treatment and 8 h of cadmium chloride treatment (begun 4 h after anti-IgG treatment). Expression of p53 was quantitated by using antibody DO-1 (top), expression of Z was quantitated by using antibody BZ.1 (middle), and expression of the EA-D complex was quantitated by using antibody 9240 In contrast, immunocompromised patients (in particular organ transplant recipients and patients with AIDS) have a high frequency of EBV-associated lymphomas, and in these patients, up to 60% of EBV-positive lymphomas contain cells expressing the Z protein (46). Z is also expressed in a small percentage of nasopharyngeal carcinoma cells (7) and in Reed-Sternberg cells of EBV-positive Hodgkin's disease (47).…”

RECK is a target of Epstein–Barr virus latent membrane protein 1

“…First, restoration of RECK expression by PD98059 reduced LMP1-induced release of active MMP-9. Second, suppression of PD98059-induced RECK expression by smallIntroduction Epstein-Barr virus (EBV), a ubiquitous human gammaherpesvirus, is implicated in the etiology of human malignancies, such as Burkitt's lymphoma, Hodgkin's disease and nasopharyngeal carcinoma (NPC) (Kieff and Liebowitz, 1990;Pallesen et al, 1991;Weiss et al, 1991). The association of EBV with NPC is established by the findings that EBV DNA, RNA and proteins were detected in NPC tissues and antibodies against EBV antigens were increased in the sera of NPC patients (Kieff, 1995).…”

The expression of matrix metalloproteinase 9 is enhanced by Epstein–Barr virus latent membrane protein 1

“…EBV, the causative agent of infectious mononucleosis and oral hairy leukoplakia of the tongue, is also associated with a variety of malignancies such as Burkitt lymphoma (BL) (24), as well as Hodgkin's disease (25), NPC (26), and lymphoproliferative disease in organ-transplant recipients and in patients with AIDS (27). The majority of tumor cells, regardless of type, are latently infected.…”