Peroxisome proliferator-activated receptor and AMP-activated protein kinase agonists protect against lethal influenza virus challenge in mice.
BACKGROUND
A novel influenza A (H1N1) virus was isolated from humans in North America and has developed into the first pandemic of the 21st century. Reports of a global shortage of antiviral drugs, the evolution of drug-resistant influenza virus variants, and a 6-month delay in vaccine availability underline the need to develop new therapeutics that may be widely distributed during future pandemics.


METHODS
In an effort to discover alternatives to the conventional therapeutic strategies available, we screened several classes of immunomodulatory agents possessing the potential to mitigate the effects of influenza virus-induced immunopathology.


RESULTS
Here, we provide preliminary evidence that two classes of drugs, peroxisome proliferator-activated receptor-gamma agonists and AMP-activated protein kinase agonists, provide protection in mice infected with highly pathogenic and pandemic strains of influenza virus.


CONCLUSIONS
The extensive production in the developed world, combined with the significant degree of protection described here, establishes these drugs as a potential therapeutic option that may be broadly implemented to combat serious disease caused by future influenza epidemics or pandemics.
Moseley
Carson E
CE
Division of Virology, Department of Infectious Diseases, St. Jude Children's Research Hospital, Memphis, TN 38105, USA.
Webster
Robert G
RG
Aldridge
Jerry R
JR
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001835:Body Weight; D005260:Female; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects / Q000472:pathogenicity; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000517:prevention & control* / Q000821:virology; D047492:Peroxisome Proliferator-Activated Receptors / Q000819:agonists*; D016019:Survival Analysis
D007155:Immunologic Factors; D047492:Peroxisome Proliferator-Activated Receptors; D055372:AMP-Activated Protein Kinases