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Influenza infection of humans remains an important public health problem. Vaccine strategies result in a significant but only partial control (65–85%) of infection. Thus, chemotherapeutic approaches are needed to provide a solution both for vaccine failures and to limit infection in the unvaccinated population. Previously (Walsh et al., 2011; Teijaro et al., 2011) documented that sphingosine-1-phosphate...
The cytokine storm is an aggressive immune response characterized by the recruitment of inflammatory leukocytes and exaggerated levels of cytokines and chemokines at the site of infection. Here we review evidence that cytokine storm directly contributes to the morbidity and mortality resulting from influenza virus infection and that sphingosine-1-phosphate (S1P) receptor agonists can abort cytokine...
TLR7 is an innate signaling receptor that recognizes single-stranded viral RNA and is activated by viruses that cause persistent infections. We show that TLR7 signaling dictates either clearance or establishment of life-long chronic infection by lymphocytic choriomeningitis virus (LCMV) Cl 13 but does not affect clearance of the acute LCMV Armstrong 53b strain. TLR7 −/− mice infected with...
Cytokine storm during viral infection is a prospective predictor of morbidity and mortality, yet the cellular sources remain undefined. Here, using genetic and chemical tools to probe functions of the S1P 1 receptor, we elucidate cellular and signaling mechanisms that are important in initiating cytokine storm. Whereas S1P 1 receptor is expressed on endothelial cells and lymphocytes...
Initial and early tissue injury associated with severe influenza virus infection is the result of both virus-mediated lysis of infected pulmonary cells coupled with an exuberant immune response generated against the virus. The excessive host immune response associated with influenza virus infection has been termed “cytokine storm.” Therapies that target virus replication are available; however, the...
There is no known antiviral drug treatment that routinely terminates persistent virus infections. A recent provocative report indicated that low dosage of the sphingosine analog FTY720 caused lymphopenia in mice persistently infected with lymphocytic choriomeningitis virus (LCMV)-clone 13 (Cl 13) and induced viral clearance within 30 days post-treatment (Premenko-Lanier et al., 2008). However, we...
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