The interplay between nidoviruses and the infected host cell was investigated. Arterivirus RNA-synthesising activity was shown to depend on intact membranes and on a cytosolic host protein which... Show moreThe interplay between nidoviruses and the infected host cell was investigated. Arterivirus RNA-synthesising activity was shown to depend on intact membranes and on a cytosolic host protein which does not cosediment with the RTC. Furthermore, the immunosuppressant drug cyclosporin A (CsA) blocks replication of EAV and the swine arterivirus PRRSV in cell culture. Cyclophilin A appears to be an important host factor for EAV replication. CsA may be a nidovirus-wide inhibitor of replication since this compound also blocked replication of the coronaviruses SARS-CoV, HCoV-229E, and MHV. We further described a kinase siRNA library screen that identified ninety antiviral and forty proviral hits and signalling pathways involved in the SARS-CoV replicative cycle. PKR (antiviral) and COPB2 (proviral) were validated in follow-up experiments. We also investigated MERS-CoV replication characteristics and we described an assay t o screen for compounds that block MERS-CoV infection. CsA and pegylated IFN-_ (PEG-IFN) significantly inhibited infection, and MERS-CoV was shown to be much more sensitive to PEG-IFN treatment than SARS-CoV, an observation that may have implications for the treatment of MERS-CoV infection. The data presented in this thesis might contribute to better understand virus replication and hopefully provide additional starting points for the development of antiviral strategies. Show less