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  • Title: Epstein-Barr virus latent gene expression during the initiation of B cell immortalization.
    Author: Allday MJ, Crawford DH, Griffin BE.
    Journal: J Gen Virol; 1989 Jul; 70 ( Pt 7)():1755-64. PubMed ID: 2544663.
    Abstract:
    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 extrachromosomal 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.
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