Epstein-Barr Virus Latent Gene Expression during the Initiation of B Cell Immortalization
Department of Virology, Royal Postgraduate Medical School, Du Cane Road, London W12 0NN, U.K. Epstein-Barr virus (EBV) has the capacity to immortalize a subpopulation of resting B lymphocytes. Lymphoblastoid cell lines (LCL) established in this way carry the latent EBV genome as multiple copies of a...
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Published in | Journal of general virology Vol. 70; no. 7; pp. 1755 - 1764 |
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Main Authors | , , |
Format | Journal Article |
Language | English |
Published |
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Soc General Microbiol
01.07.1989
Society for General Microbiology |
Subjects | |
Online Access | Get full text |
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Summary: | Department of Virology, Royal Postgraduate Medical School, Du Cane Road, London W12 0NN, U.K.
Epstein-Barr virus (EBV) has the capacity to immortalize a subpopulation of resting B lymphocytes. Lymphoblastoid cell lines (LCL) established in this way carry the latent EBV genome as multiple copies of an extrachromasomal episome. Viral gene expression in LCLs is highly restricted; products identified correspond to a membrane protein (latent membrane protein; LMP), a nuclear antigen complex (Epstein-Barr nuclear antigens; EBNAs 1 to 6), two small RNA species (EBERs 1 and 2) and RNA species thought to encode a second membrane-associated polypeptide designated terminal protein (TP). Here we have investigated the temporal sequence of expression of the characterized latent proteins during the initiation of immortalization when resting B cells are stimulated to enter and traverse the cell cycle. The analysis has been carried out on prolymphocytic leukaemia cells infected in vitro with either the immortalizing B95-8 strain of virus or the non-immortalizing P3HR1 strain. The results reveal that following B95-8 infection, a sequence of EBV expression is initiated within approximately 8 h with the synthesis of detectable levels of EBNA 2 shortly followed by EBNAs 1, 3, 4, 5 and 6. There is then a delay of approximately 40 h until the expression of LMP completes the latent pattern of proteins found in LCLs. P3HR1 infection, however, produces only transient expression of some EBNA species in a small percentage of cells after approximately 48 h. These observations suggest the failure of P3HR1 virus to immortalize may not be due solely to the absence of EBNA 2 expression and that cellular and/or virus-mediated events occur after EBNA synthesis which then facilitate efficient LMP expression and immortalization.
Keywords: EBV, latent gene expression, immortalization
Received 11 November 1988;
accepted 3 March 1989. |
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Bibliography: | ObjectType-Article-2 SourceType-Scholarly Journals-1 ObjectType-Feature-1 content type line 23 ObjectType-Article-1 ObjectType-Feature-2 |
ISSN: | 0022-1317 1465-2099 |
DOI: | 10.1099/0022-1317-70-7-1755 |