From our 20 year long experience of working on the γ-herpesvirus KSHV, we learned a lot about how the virus manages to establish such a long-lasting infection, to escape the detection by the immune system of the host and yet to be transferred from mother to daughter cell during cell division. In doing so, we concentrated on a particular viral protein, the latency-associated nuclear antigen LANA, which mediates many of these functions and can also reprogram the infected cell for the benefit of the virus (e.g. Rainbow et al., 1997, Platt et al., 1999; Ottinger et al., 2006, 2009; Viejo-Borbolla et al., 2003, 2005; Jäger et al., 2012; Zhang et al., 2016; Mariggio et al., 2017). An important aspect of our work is to understand the structure of LANA (Hellert et a., 2013, 2015) and the nature of tiny ‘territories’ in the nucleus of the infected cell in which the virus resides in a latent form. Over the last 20 years we have also characterized the function of a viral non-structural membrane protein, pK15, which is necessary during the early stages of productive early replication and initiates intracellular signaling pathways required for viral replication. For both LANA and pK15 we have, in collaboration with another RESIST scientist, M. Empting, developed first generation small molecule inhibitors that antagonize the function of LANA or pK15-dependent signal transduction. Within RESIST we want to transfer our gained knowledge and experience from the work on KSHV LANA to other herpesviruses, such as the β-herpesvirus HCMV. We seek to find ‘weak spots’ in the interaction between the virus and the infected cell and to target these spots with novel and more efficient antiviral drugs.