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

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

Type I IFNs signaling through its receptor leads to transcription of many interferon responsive genes (ISGs) that limit the virus replication and enhance the immune response. Secreted type I IFNs signal through the IFN-α/β receptor complex (IFNAR), composed of two transmembrane protein subunits, IFNAR1 and IFNAR2, which are present on the surface of every nucleated cell. Sensing of type I IFNs can enhance the production of type I IFNs and other inflammatory cytokines [52, 53] . The dimerization of the two subunits of the IFNAR with IFN- or IFN- leads to activation of the intracellular kinases Jak1 and Tyk2, which phosphorylate the STAT transcription factors leading to the generation of STAT homodimers (STAT1) and heterodimers (STAT1 with STAT2). Phosphorylated STAT1 and STAT2, together with IRF-9, form a complex called interferon-stimulated gene factor 3 (ISGF3) that translocates to the nucleus and activates the transcription of ISGs [54] (Figure 1 ).