Gap junctions provide an essential means of intercellular communication in multicellular organisms and serve a crucial role in the intercellular spread of molecular information from virus-infected cells to adjacent cell to curtail infection, including antiviral messengers that trigger interferon responses and viral peptides that may be cross-presented via MHC class I to cytotoxic T lymphocytes. Despite the importance of gap junctions in antiviral responses, very little is known regarding possible viral modulation of gap junction intercellular communication. Recently, we have generated breakthrough data in this domain, showing that the alphaherpesvirus pseudorabies virus triggers phosphorylation of the central gap junction component connexin 43 (Cx43) via the viral pUL46 and pUS2 proteins and the ERK1/2 signaling pathway, resulting in gap junction closure. Importantly, we found that virus-induced closure of gap junctions increases intercellular virus spread. These exciting data put us in an internationally unique position to unravel for the first time the detailed molecular mechanism underlying virus-induced Cx43 phosphorylation and gap junction closure, and its consequences for the antiviral immune response, which will allow to design to design novel gap junction-targeted antiviral strategies. Our approach will include a.o. technically challenging but highly relevant in vitro and ex vivo models as well as high-end techniques (e.g. photoporation, super resolution microscopy).