The overall objective of this research is to do a systematic study of (a) coronavirus molecular structure and (b) the molecular biology of coronavirus replication. While the coronaviruses now appear to make up one of 10 families of animal RNA viruses, little is known of how they replicate. It is not known, for example, (a) by what mechanism they can establish persistent infections, (b) what the total range of host immune responses to them are, or (c) whether there might be unique enzymes in their system of replication that would be amenable to inhibition by chemotherapy. The bovine coronarvirus which causes neonatal diarrhea, the hemagglutinating encephalomyelitis virus of swine, and the transmissible gastroenteritis virus of swine, all of which can be cultured to high titers in tissue cultures, will be purified by sucrose gradient sedimentation and structurally analyzed. Radioactively labeled polypeptides, glycopolypeptides, and ribonucleic acids, will be analyzed using gel electrophoresis. A virion associated RNA-dependent RNA polymerase will be sought. Virion RNA, intracellular virus-specific RNA, and polymerase product (if found) will be analyzed for size, strandedness (single or double), polyadenylation, and a 5'-methylated cap structure of the type in m7G5'ppp5'Nmp... While it has been known for a number of years that human coronaviruses are a cause of respiratory disease, they have only recently been associated with human gastrointestinal diseases. This association requires further investigation in view of the fact that many neonatal diarrheas and gastrointestinal diseases in a variety of lower animal species are caused by coronaviruses. One porcine coronavirus is implicated in a zoonotic association with a human chronic nephropathic condition and this requires further investigation. We view the coronaviruses as a unique and important group of pathogens and that a careful molecular analysis of structure and replication will contribute to a fundamental understanding of pathogenesis and host responses.