scholarly journals Epstein-Barr virus in Burkitt’s lymphoma: A role for latent membrane protein 2A

Cell Cycle ◽  
2010 ◽  
Vol 9 (5) ◽  
pp. 901-908 ◽  
Author(s):  
Kathryn T. Bieging ◽  
Michelle Swanson-Mungerson ◽  
Alexandra C. Amick ◽  
Richard Longnecker
2007 ◽  
Vol 88 (5) ◽  
pp. 1454-1459 ◽  
Author(s):  
Markus P. Rechsteiner ◽  
Christoph Berger ◽  
Matthias Weber ◽  
Jürg A. Sigrist ◽  
David Nadal ◽  
...  

Epstein–Barr virus (EBV) latent membrane protein 2A (LMP2A) blocks B-cell receptor (BCR) signalling after BCR cross-linking to inhibit activation of lytic EBV, and ectopically expressed LMP2B negatively regulates LMP2A. Here, it is demonstrated that silencing of LMP2B in EBV-harbouring Burkitt's lymphoma Akata cells results in reduced expression of EBV immediate-early lytic BZLF1 gene mRNA and late lytic gp350/220 protein upon BCR cross-linking. Similarly, reduction of lytic EBV activation was observed in Akata cells overexpressing LMP2A. In contrast, silencing of LMP2A expression resulted in higher lytic EBV mRNA and protein expression in BCR cross-linked Akata cells. These observations indicate a role for LMP2B distinct from that of LMP2A in regulation of lytic EBV activation in the host cell and support the hypothesis that LMP2B exhibits a negative-regulatory effect on the ability of LMP2A to maintain EBV latency by preventing the switch to lytic replication.


Blood ◽  
1997 ◽  
Vol 90 (4) ◽  
pp. 1664-1672 ◽  
Author(s):  
G. Niedobitek ◽  
E. Kremmer ◽  
H. Herbst ◽  
L. Whitehead ◽  
C.W. Dawson ◽  
...  

We describe two new monoclonal antibodies specific for the Epstein-Barr virus (EBV)-encoded latent membrane protein 2A (LMP2A) that are suitable for the immunohistochemical analysis of routinely processed paraffin sections. These antibodies were applied to the immunohistochemical detection of LMP2A in Hodgkin's disease (HD). LMP2A-specific membrane staining was seen in the Hodgkin and Reed-Sternberg (HRS) cells of 22 of 42 (52%) EBV-positive HD cases, but not in 39 EBV-negative HD cases. In lymphoid tissues from patients with acute infectious mononucleosis (IM), interfollicular immunoblasts were shown to express LMP2A. This is the first demonstration of LMP2A protein expression at the single-cell level in EBV-associated lymphoproliferations in vivo. The detection of LMP2A protein expression in HD and IM is of importance in view of the proposed role of this protein for maintaining latent EBV infection and its possible contribution for EBV-associated transformation. Because LMP2A provides target epitopes for EBV-specific cytotoxic T cells, the expression of this protein in HRS cells has implications for the immunotherapeutic approaches to the treatment of HD.


Author(s):  
D. N. Misra ◽  
R. M. Agostini ◽  
E. J. Yunis

Epstein-Barr virus (EBV) infection, prevalent in all human populations, is clinically silent in general, but causes infectious mononucleosis in some adolescents and B-lymphocyte proliferative disorders (LPDs) in immunocompromised individuals (e.g. AIDS infected; allograft recipients). EBV is also etiologically associated with African Burkitt’s lymphoma, nasopharyngeal carcinoma, and Hodgkin’s disease. The virus infects B lymphocytes and transforms them into lymphoblastoid cells which proliferate indefinitely in culture. The latently infected cells express an array of EBV gene products including 6 nuclear antigens (EBNAs), terminal proteins LMP-2A and LMP-2B, latent membrane protein LMP-1, and untranslated RNAs EBER 1 and EBER 2. These components are being extensively studied since they are involved in latency or proliferative transformation; LMP-1 has also shown oncogenic properties. In this work, we have used immunogold electron microscopy for precise subcellular localization of LMP-1 in EBV infected cell lines.Two human cell lines, P3HR-1 (Burkitt’s lymphoma) and CCL-113 (Hodgkin’s disease), obtained from ATCC, were grown in RPMI 1640 containing 20% fetal calf serum, 100 U/ml penicillin and 100 μg/ml streptomycin.


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