Editorial: Signal transduction by viral factors: critical interface between the virus and its host cell with implications for the viral life cycle and disease development

The interaction of viral factors with cellular signal transduction pathways is a central interface between the virus and its host cell. Viruses have learned to exploit cellular signaling molecules for their own purposes, the establishment of the viral life cycle and propagation of the virus. Moreover, some viral proteins critically contribute to viral pathogenesis by deregulating the host cell signal transduction network. One example is the development of malignancies upon infection with tumor viruses. During co-evolution with the virus, the host has developed potent anti-viral strategies which are mainly based upon the detection of viral components by cellular receptors. Such sensors of a viral attack activate signal transduction pathways leading to a broad anti-viral response against the invader. This special issue of Signal Transduction focuses on molecular and functional aspects of viral interactions with host cell signaling with relevance for the anti-viral response, the viral life cycle, viral pathogenesis and cell transformation. It is further illustrated that viruses can also serve as powerful means to understand and even uncover novel aspects of cellular signal transduction pathways. Viral infections of vertebrates cause an interferon response, the primary defense line against the virus. Interferons are involved in the activation of immune cells and are important mediators of the anti-viral response by the innate and adaptive immune system. Brz zka et al. review recent developments in the field of cellular sensors of viral nucleic acids, Toll-like and RIGlike receptors, and their signal transduction pathways leading to the induction of type I interferons. They also focus on strategies developed by different viruses to escape immunosurveillance by specifically interfering with the interferon signaling network and discuss the implications for the constant battle between the virus and its host. Upon infection of target cells, some viruses boost cell proliferation to promote virus propagation. In the case of the human DNA tumor virus EBV (Epstein-Barr virus), this process can lead to the development of proliferative and even malignant diseases if EBV-infected B cells are not sufficiently controlled by the immune system. The latent membrane protein 1 (LMP1) is the major oncogene of EBV which is essential for B cell transformation by the virus. The article by Kieser describes how LMP1 highjacks a network of host cell signaling pathways of the tumor necrosis factor (TNF) and Toll-like receptor families to support EBV transformation of B cells. LMP1 antagonizes apoptosis and induces mitogenic and survival pathways by unique interactions with cellular signaling molecules such as the TNF-receptor associated death domain protein (TRADD). The Tax protein of the human T cell leukemia virus type 1 (HTLV-1), a delta-retrovirus causing an aggressive malignancy of human T cells, is another example of a potent viral oncoprotein that establishes multiple interactions with the host cell signaling machinery. Silbermann and Grassmann review current knowledge on how Tax controls survival, proliferation and genomic stability of the target cell. By cross-talking to transcriptional pathways such as NF-jB and AP1, regulation of cytokine signaling and anti-apoptotic factors as well as the direct targeting of cell cycle regulators, Tax deregulates T cells and critically contributes to the malignant transformation of HTLV-1 infected cells. Cellular membranes contain dynamic subdomains, named membrane lipid rafts, which are characterized by a high content of cholesterol, sphingolipids and an altered composition of proteins. Membrane lipid rafts play an important role in the regulation of signal transduction processes by many cellular receptors such as the T cell receptor (TCR). Not surprisingly, viruses exploit Signal Transduction 2007, 7, 3 –4 S. Labib et al. 3