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Many of the currently established concepts and consequences about viruses and immunologic tolerance, virus-induced immunosuppression, virus-induced autoimmunity, immune complex disease, and virus\u2013lymphocyte and virus\u2013dendritic cell interactions evolved through studies of LCMV in its natural murine host. Similarly, the mechanisms, aftermath, and treatment of persistent RNA viruses emerged, in large part, from research on LCMV. Analysis of acute influenza virus infections uncovered the prominent direct role that cytokine storm plays in the pathogenesis, morbidity, and mortality from this disease. Cytokine storm of influenza virus infection is initiated via a pulmonary endothelial cell amplification loop involving IFN-producing cells and virus-infected pulmonary epithelial cells. Importantly, the cytokine storm is chemically treatable with specific agonist therapy directed to the sphingosphine 1 phosphate receptor 1, which is located on pulmonary endothelial cells, pointing to the endothelial cells as the gatekeepers of this hyperaggressive host immune response.<\/jats:p>","DOI":"10.1073\/pnas.1222025110","type":"journal-article","created":{"date-parts":[[2013,1,23]],"date-time":"2013-01-23T02:27:25Z","timestamp":1358908045000},"page":"4180-4183","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":32,"title":["Lessons learned and concepts formed from study of the pathogenesis of the two negative-strand viruses lymphocytic choriomeningitis and influenza"],"prefix":"10.1073","volume":"110","author":[{"given":"Michael B. 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