Since EBV infected B cells can be sustained in vitro in the absence of EBNA3A and EBNA3C by CD40L mediated CD40 engagement, we suggest that the microenvironment of secondary lymphoid tissues, possibly via CD40L on CD4+ T cells, allows for the persistence of EBNA3A and EBNA3C deficient EBV after infection. Here, CD4 is linked to infection.