Viral interactions with the Notch pathway

The Notch signaling pathway influences cell fate decisions, proliferation versus differentiation and cell survival. Viruses both utilize and manipulate the differentiation state of infected cells, promote or block cell cycling and employ a variety of mechanisms to evade innate cellular anti-viral responses and promote cell survival. In light of these commonalities, it is perhaps not surprising that several viruses have tapped into the Notch pathway to advance their own life cycles. This first became apparent from studies showing targeting of Epstein-Barr virus proteins to the nuclear effector of Notch signaling CSL (CBF1/RBPJk). More recently the Kaposi's sarcoma-associated herpesvirus RTA protein has been found to bind CSL. Notch pathway interactions have also been described for adenovirus SV40 and human papilloma virus. This review focuses on the herpesvirus protein interactions with the Notch pathway and the insights that these interactions have provided.