期刊
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
卷 110, 期 11, 页码 4180-4183出版社
NATL ACAD SCIENCES
DOI: 10.1073/pnas.1222025110
关键词
viral persistence; immunosupression
资金
- National Institutes of Health [R01 AI-09484, U01 AI 074564, U54 AI057160]
Viruses have unique lifestyles. To describe the pathogenesis and significance of viral infection in terms of host responses, resultant injury, and therapy, we focused on two RNA viruses: lymphocytic choriomeningitis (LCMV) and influenza (Flu). Many of the currently established concepts and consequences about viruses and immunologic tolerance, virus-induced immunosuppression, virus-induced autoimmunity, immune complex disease, and virus-lymphocyte and virus-dendritic 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 gate-keepers of this hyperaggressive host immune response.
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