Influenza A viruses are a major cause of mortality. Given the potential for future lethal pandemics, effective drugs are needed for the treatment of severe influenza such as that caused by H5N1 viruses. Using mediator lipidomics and bioactive lipid screen, we report that the omega-3 polyunsaturated fatty acid (PUFA)-derived lipid mediator protectin D1 (PD1) markedly attenuated influenza virus replication via RNA export machinery. Production of PD1 was suppressed during severe influenza and PD1 levels inversely correlated with the pathogenicity of H5N1 viruses. Suppression of PD1 was genetically mapped to 12/15-lipoxygenase activity. Importantly, PD1 treatment improved the survival and pathology of severe influenza in mice, even under conditions where known antiviral drugs fail to protect from death. These results identify the endogenous lipid mediator PD1 as an innate suppressor of influenza virus replication that protects against lethal influenza virus infection.

Receiver operating characteristic (ROC) curve for the composite classification algorithm. All curves presented are the median of 1000 repeat crossvalidations. Extended Data Fig. 6 Extended Data Fig. 7 Extended Data Fig. 8 Extended Data Fig. 9 Extended Data Fig. 10 Delete rows as needed to accommodate the number of figures (10 is the maximum allowed). 2. Supplementary Information: A. Flat Files Complete the Inventory below for all additional textual information and any additional Supplementary Figures, which should be supplied in one combined PDF file. Item Present? Filename This should be the name the file is saved as when it is uploaded to our system, and should include the file extension. The A brief, numerical description of file contents.

CXCL10-CXCR3 signaling appears to be a critical factor for the exacerbation of the pathology of ARDS. Thus, the CXCL10-CXCR3 axis could represent a prime therapeutic target in the treatment of the acute phase of ARDS of nonviral and viral origins.

The ionic structure of organic electrolyte solutions has been investigated, by means of Raman spectroscopy for mixed aprotic solvents that dissolve lithium salts. The solutions consisted of binary solvent systems of a high permittivity solvent (ethylene carbonate, EC) mixed with low viscosity alkyl carbonates (dimethyl carbonate, DMC, and diethyl carbonate, DEC) or a linear alkyl ether (1,2-dimethoxyethane, DME) and of LiCF 3 SO 3 , and as the solute. The Raman shifts based on the solvents varied with the sort of) 2 dissolved lithium salts and their concentration. The ion solvation was estimated from the side-bands of the Raman scattering for the CwO stretch of single bonds of the carbonate groups and for the symmetric ring deformation of EC. The number of EC molecules interacting with the lithium cation (Li`) was higher than that of DMC in a mixed EC ] DMC (50 : 50 by volume) system. The apparent solvation number of Li`in 1.5 mol dm~3 solution was about 2.8 in EC ] DMC, whereas that in 1.5 M solution was LiCF 3 SO 3 LiPF 6 about 3.9. SpeciÐc solvation of Li`was distinguished in EC ] DME (50 : 50), where DME predominantly coordinates to Li`. However, it was also conÐrmed that EC, which has a lower donicity, interacts with Liè ven in the EC ] DME system. That is, the solvation number of EC in remained LiCF 3 SO 3 /(EC ] DME) ca. 1.0 even in high salt concentrations.

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