Host cell requirements for efficient infection of quiescent primary B lymphocytes by Epstein-Barr virus

Quiescent primary B lymphocytes are efficiently immortalized by Epstein-Barr virus (EBV). This process requires both the delivery and expression of the viral genome and results in activation of the cell division cycle. Infection of B lymphocytes depends on a direct interaction between the viral glycoprotein gp340/220 and CD21, the C3dg complement receptor. This interaction is required for the adsorption of EBV. In addition, several lines of evidence suggest that the interaction of EBV with CD21 modulates the phenotype of cells. CD21 forms part of a multimeric signal transduction complex with CD19, TAPA-1, and Leu-13. In normal B lymphocytes, CD19 becomes tyrosine phosphorylated following stimulation of the antigen receptor and recruits the signal-transducing enzyme phosphatidylinositol 3-kinase kinase. Here, we investigated the involvement of signal transduction pathways in efficient infection. Protein synthesis is not required for events leading to the transcription of the viral genome, suggesting that the early stages of infection do not depend on the expression of novel cell genes and consistent with the Wp promoter being the first viral promoter used upon infection. Since the stimulation of cells with gp340/220 leads to an increase in the level of CD19 tyrosine phosphorylation, we investigated the potential contribution of both tyrosine and phosphatidylinositol 3-kinase kinases to efficient infection. Both kinases contribute to the posttranscriptional control of viral gene expression following infection, but neither is required for the entry or initial transcription of the virus. Thus, it appears that EBV exploits a host signal transduction pathway to efficiently infect primary cells.