The normal cell cycle activation program is exploited during the infection of quiescent B lymphocytes by Epstein-Barr virus.
B lymphocytes in the peripheral circulation are maintained in a non-proliferative state. Antigen recognition stimulates limited proliferation, whereas infection with Epstein-Barr virus (EBV) results in continual proliferation and the outgrowth of immortal cell lines. Because it is not clear at which point in cell cycle the peripheral B lymphocytes are arrested, we characterized the expression of several cell cycle-associated genes in quiescent and stimulated cells. We show that the expression of four cell genes, cdc-2, cyclin E, CD23, and cyclin D2, are up-regulated approximately 100-fold as a result of EBV-mediated immortalization. Because these genes play a positive role in cell proliferation, we suggest that this regulatory switch contributes to controlling entry into the cell cycle. Transient stimulation of quiescent B lymphocytes with either a cocktail of anti-CD40, anti-IgM, and IL4, or EBV results in the rapid expression of the same four genes, suggesting that, after infection, EBV exploits the normal program of B-lymphocyte cell cycle activation.
Hollyoake
M
M
Ludwig Institute for Cancer Research, St. Mary's Hospital Medical School, London.
Stühler
A
A
Farrell
P
P
Gordon
J
J
Sinclair
A
A
D000328:Adult; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology* / Q000821:virology*; D001483:Base Sequence; D002453:Cell Cycle / Q000502:physiology; D018797:Cell Cycle Proteins; D002478:Cells, Cultured; D056742:Cyclin D2; D016213:Cyclins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005786:Gene Expression Regulation / Q000502:physiology; D018816:Genes, cdc; D016259:Genes, myc; D006566:Herpesviridae Infections / Q000097:blood*; D004854:Herpesvirus 4, Human; D006801:Humans; D008213:Lymphocyte Activation; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D012313:RNA / Q000097:blood / Q000235:genetics; D012333:RNA, Messenger / Q000097:blood / Q000235:genetics; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics; D015854:Up-Regulation / Q000502:physiology
C080336:CCND2 protein, human; D018797:Cell Cycle Proteins; D056742:Cyclin D2; D016213:Cyclins; D004268:DNA-Binding Proteins; C064352:MYBL2 protein, human; D012333:RNA, Messenger; D015534:Trans-Activators; D014157:Transcription Factors; D012313:RNA