Buying Time—The Immune System Determinants of the Incubation Period to Respiratory Viruses

Hermesh, Tamar; Moltedo, Bruno; López, Carolina B.; Moran, Thomas M.

The inflammasome complex is required to generate the active form of the cytokines IL-1β, IL-18 and IL-33. The production of these cytokines requires two signals. Signal one is given by recognition of viral RNA as described above. This leads to increased levels of cytokines mRNA. Signal two activates the inflammasome and is sensed by NLRP3. NLRP3 is activated after exposure to ATP, dsRNA, poly I:C and various crystals such as monosodium urate [44] [45] [46] [47] .In order to produce activated cytokines, pro-IL-1β, pro-IL-18 and pro-IL-33 must be cleaved by caspase-1. Caspase-1 is part of the inflammasome complex that contains NLRP3 and the adapter apoptosis-associated speck-like protein containing a CARD (ASC) [48] . It has been shown that the NLRP3 inflammasome is required for the production of IL-1β and IL-18 during influenza infection in vivo [49] . It remains unclear whether the inflammasome physically senses these compounds. Recently it was suggested that influenza virus M2, an ion channel, causes changes in ionic concentration in cellular compartments which lead to NLRP3 activation [50] . Figure 1 . Viral antagonism to type I IFN induction and signaling. Many pathogenic viruses are able to inhibit the host cell ability to detect infection through the TLR and RLR pathways, thereby inhibiting the production of type I IFNs and other cytokines. Some viruses are also able to inhibit type I IFNs signaling.