B Induction

Epstein-Barr virus (EBV), an oncogenic human herpesvirus, binds to and infects normal human B lymphocytes via CD21, the CR2 complement receptor. Studies of the mechanisms that en-able EBV to infect nonactivated, noncycling B cells provide compelling evidence for a se-quence of events in which EBV binding to CD21 on purified resting human B cells rapidly ac-tivates the NF-k B transcription factor, which, in turn, binds to and mediates transcriptional activation of Wp, the initial viral latent gene promoter. Thus, EBV binding to its cellular re-ceptor on resting B cells triggers an NF-k B–dependent intracellular signaling pathway which is required for infection. I nfection of normal human B lymphocytes by EBV, a ubiquitous transforming human herpesvirus with onco-genic potential, is initiated by binding of the virus to CD21 (CR2, complement receptor type 2), the receptor for C3dg, the terminal activation/processing fragment of the third complement component (1, 2). EBV binds to CD21 via a short primary sequence epitope in the major viral envelope glycoprotein (gp350/220), which is homologous in se-quence to the binding epitope in C3dg (3). CD21 is a mem-ber of an intracellular signaling pathway which modulates B cell activation, growth, and differentiation (1, 2). Unlike most viruses, EBV infects nonactivated, resting cells. In the present study, we evaluated the hypothesis that an intracel-lular signaling pathway initiated by EBV binding to CD21 enables EBV to infect resting B cells. Prominent among the signaling pathways that rapidly convert extracellular signals into changes in gene expression is the NF-