A. Objectives. The objective of this small grant were to was to investigate the regulation of PRRSV infection in cultured pig macrophages. The purpose of the work was to learn more about how PRRSV infects and spreads through cultured cells, and also to study the effects of antiviral agents on the virus. The results should help in the design of future PRRS treatments. B. Methods. The research was conducted utilizing cells obtained from pig lungs (also known as porcine alveolar macrophages or PAMs). These cells were exposed to PRRSV under appropriate laboratory conditions, and the course of PRRSV infection was studied by a sensitive microscopy technique. Different antiviral treatments were applied to the cells in order to determine antiviral strategies which might work in pigs. C. Research findings. From our research, PRRSV was found to replicate efficiently in some but not all PAMs, suggesting the physiological state of the target cells may regulate resistance to the virus. Consistent with this possibility, the course of infection was dramatically different in PAMs compared to that in another laboratory cell line (MARC-145 cells), since PRRSV was automatically down-regulated in PAMs after a relatively short period in culture. PRRSV infection of PAMS was found to be highly susceptible to antiviral treatment with two particular classes of drugs (proteins called cytokines which activate pig cell resistance to virus infection; and antibiotic molecules called quinolones). The two classes of drugs synergized to enhance pig cell resistance to PRRSV infection. These results are all consistent with the ability of pig macrophages to elaborate a natural resistance to PRRSV infection, which can also be induced by drug treatment. The funded research was included in a peer-reviewed publication, one national presentation, and one invention disclosure report. D. Significance for industry. The results of this project describe a potentially important approach to prevention and/or treatment of PRRSV infection, based on regulation of cellular permissiveness to the virus. Drug synergy between antiviral cytokines and quinolones suggests a specific direction for the development of drug therapy for PRRS which might have acceptable toxicity (i.e. reduced side-effects) in pigs. Future research based on this pilot project could conceivably lead to effective preventive or therapeutic drugs for PRRS, as well as expand our knowledge of PRRSV regulation.