CD40 signaling activated by Epstein–Barr virus promotes cell survival and proliferation in gastric carcinoma-derived human epithelial cells

CD40 signaling plays a critical role in the survival and proliferation of EBV-infected lymphocytes. Here we show that CD40 is constitutively expressed in the human gastric carcinoma-derived cell lines AGS, MKN28, and MKN74, and expression of CD40L is induced by in vitro infection with EBV. Blocking the interaction between CD40 and CD40L with CD40Ig, a fusion protein of CD40 and IgG, impaired proliferation of EBV-infected AGS cells and enhanced their calcium ionophore-induced apoptosis. These results suggest that CD40 signaling plays a critical role in the survival and proliferation of EBV-infected epithelial cells, as well as in the virus-infected lymphocytes.