protectin-d1 and Orthomyxoviridae-Infections

Inflammation is generally accepted as a component of the host defence system and a protective response in the context of infectious diseases. However, altered inflammatory responses can contribute to disease in infected individuals. Many endogenous mediators that drive the resolution of inflammation are now known. Overall, mediators of resolution tend to decrease inflammatory responses and provide normal or greater ability of the host to deal with infection. In the lung, it seems that pro-resolution molecules, or strategies that promote their increase, tend to suppress inflammation and lung injury and facilitate control of bacterial or viral burden. Here, we argue that the demonstrated anti-inflammatory, pro-resolving, anti-thrombogenic and anti-microbial effects of such endogenous mediators of resolution may be useful in the treatment of the late stages of the disease in patients with COVID-19.

Topics: Acetates; Angiotensin I; Animals; Annexin A1; Anti-Inflammatory Agents; COVID-19; COVID-19 Drug Treatment; Disease Models, Animal; Docosahexaenoic Acids; Humans; Hydrogen Peroxide; Inflammation; Inflammation Mediators; Mice; Orthomyxoviridae Infections; Oxidants; Peptide Fragments; Peptides; Phosphodiesterase 4 Inhibitors; Pneumonia, Viral; Rolipram; Vasodilator Agents

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.

Topics: Active Transport, Cell Nucleus; Animals; Cell Line; Docosahexaenoic Acids; Humans; Influenza A Virus, H1N1 Subtype; Influenza A Virus, H5N1 Subtype; Mice; Orthomyxoviridae Infections; Virus Replication

Topics: Active Transport, Cell Nucleus; Animals; Docosahexaenoic Acids; Humans; Influenza A virus; Mice; Orthomyxoviridae Infections; Virus Replication