Virus infections remain a major threat to human and animal health. They have a huge impact on global economies and account for a substantial part of healthcare costs worldwide. RNA viruses are of particular interest because their replication machinery lacks proofreading activity, resulting in high numbers of nucleotide misincorporations during viral genome replication and the generation of viral “quasispecies”, genetically diverse virus populations containing large numbers of variants that differ from one another in one or more position(s) of the genome sequence. Due to their error-prone polymerases and the resulting genome plasticity, RNA viruses are able to adapt quickly to changing environmental conditions by selecting variants that replicate more efficiently under new conditions (or in new hosts). The CRC 1021 investigates RNA viruses from different families including highly pathogenic (often zoonotic) viruses causing, for example, hemorrhagic fever, encephalitis or acute respiratory distress syndrome. Research in the CRC 1021 is performed in three major project areas: (i) synthesis and metabolism of viral RNA, (ii) viral factors determining pathogenicity, and (iii) cellular responses to RNA virus infections and viral factors that counteract or help escape these cellular responses. The planned studies are based on the extensive RNA virus expertise available in this consortium as well as advanced methods and tools suitable to study these viruses, including genetically closely related viruses with fundamentally different pathogenic properties in specific hosts. The CRC 1021 will use state-of-the-art technologies (involving genomics and proteomics analyses) to obtain new insight into fundamental aspects of RNA virus replication as well as the diverse and dynamic interactions of viral factors with cellular pathways and regulatory networks that operate at the virus-host interface and determine the pathogenicity of RNA viruses in humans and animals. To achieve these goals, the CRC 1021 will take a multi-disciplinary approach, bringing together scientists with extensive expertise in RNA virus research and scientists from related and/or complementary disciplines, such as Immunology, Cellular Biology, Allergology, Pharmaceutical Sciences, and Pharmacology.