Influenza, also known as the flu, is a respiratory illness caused by viruses belonging to the family Orthomyxoviridae. Influenza viruses cause severe upper respiratory illness in children and the elderly during seasonal epidemics. Influenza viruses from zoonotic reservoirs can also cause pandemics with significant loss of life in all age groups. Although vaccination is one of the most effective methods to protect against seasonal epidemics, seasonal vaccines vary in efficacy, can be ineffective in the elderly population, and do not provide protection against novel strains. Small molecule therapeutics are a critical part of our antiviral strategies to control influenza virus epidemics and pandemics as well as to ameliorate disease in elderly and immunocompromised individuals.
Influenza virus is recognized by the innate immune system by members of at least three distinct classes of PRRs (with their respective ligands indicated); the Toll-like receptors TLR3 (double-stranded RNA (dsRNA)), TLR7 (ssRNA) and TLR8 (ssRNA), retinoic acid-inducible gene I (RIG-I) (5′-triphosphate RNA) and the NOD-like receptor family member NOD-, LRR- and pyrin domain-containing 3 (NLRP3). RIG-I and NLRP3 detect virus that is present within the cytosol of infected cells (cell-intrinsic recognition), whereas TLR3 detects virus-infected cells, and TLR7 (and TLR8 in humans) detect viral RNA that has been taken up into the endosomes of sentinel cells (cell-extrinsic recognition).

References

1.Akiko Iwasaki and Padmini S. Pillai. Nat Rev Immunol. 2014 May ; 14(5): 315–328.