In summary, our high-throughput analysis of essential yeast genes identified a diverse set of host factors that affect BMV RNA replication and significantly expanded our knowledge of cellular pathways utilized by BMV. Additional studies both in yeast and in BMV's natural plant hosts should reveal how these host factors affect the virus and provide new insights to host cell function and virus-host interactions. Although targeting some essential genes may result in deleterious effects on cells or patients, focusing on the relevant cellular pathways, rather than only individual genes, may overcome such issues. For example, two of the essential genes with the most substantial inhibitory effect on BMV RNA replication, PRE1 and RPT6, are proteasome components, while other proteasome components are not essential (e.g. PRE9, identified in previous screen). Proteasome inhibitors have antiviral activity against multiple diverse viruses (including herpes simplex virus, hepatitis B virus, and HIV, among others), have been through multiple clinical trials, and are already approved for use in patients for some purposes. Many of the genes identified function in pathways utilized by other viruses and thus may present potential cellular targets for developing broad-spectrum antivirals.