Epstein-barr virus can infect B-chronic lymphocytic leukemia cells but it does not orchestrate the cell cycle regulatory proteins.
OBJECTIVE
To understand the mechanism for the refractoriness of B-chronic lymphocytic leukemia (B-CLL) cells for Epstein-Barr virus (EBV)-induced immortalization.


METHODS
Cultures were initiated with EBV-infected tonsillar B and B-CLL cells. Expression of EBNA-2 and some of the key players regulating G1/S phase transition such as c-myc expression, phosphorylation of Rb protein, expression of G1 cyclins, and the cyclin-dependent kinase inhibitor p27 were followed.


RESULTS
In line with earlier studies, EBV infection induced c-myc expression, pRb phosphorylation, D2 and D3 expression, and disappearance of p27 in normal B cells. In contrast, EBV-infected B-CLL cells remained resting and they did not express c-myc; cyclin D2, ppRb and cyclin D3 were seen only in occasional cells. Importantly, p27 expression was maintained.


CONCLUSIONS
In B-CLL cells, the expression of the EBV-encoded nuclear proteins EBNAs is not followed by entrance to the cell cycle. Thus, the difference in the interaction of EBV-normal B cells and EBV-B-CLL cells is already apparent early after infection.
Maeda
A
A
Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden. akimae@eos.ocn.ne.jp
Bandobashi
K
K
Nagy
N
N
Teramoto
N
N
Gogolák
P
P
Pokrovskaja
K
K
Székely
L
L
Björkholm
M
M
Klein
G
G
Klein
E
E
D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism*; D018797:Cell Cycle Proteins / Q000096:biosynthesis*; D002478:Cells, Cultured; D056742:Cyclin D2; D056743:Cyclin D3; D050760:Cyclin-Dependent Kinase Inhibitor p27; D016213:Cyclins / Q000096:biosynthesis; D019309:Epstein-Barr Virus Nuclear Antigens / Q000096:biosynthesis; D004854:Herpesvirus 4, Human / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood / Q000378:metabolism*; D010766:Phosphorylation; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis; D016160:Retinoblastoma Protein / Q000378:metabolism; D014407:Tumor Cells, Cultured; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis; D014764:Viral Proteins
C080336:CCND2 protein, human; C534696:CCND3 protein, human; D018797:Cell Cycle Proteins; D056742:Cyclin D2; D056743:Cyclin D3; D016213:Cyclins; C402641:EBNA-2 protein, Human herpesvirus 4; D019309:Epstein-Barr Virus Nuclear Antigens; D016271:Proto-Oncogene Proteins c-myc; D016160:Retinoblastoma Protein; D025521:Tumor Suppressor Proteins; D014764:Viral Proteins; D050760:Cyclin-Dependent Kinase Inhibitor p27