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

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

A close examination of an in vivo influenza virus infection in mice showed that the virus replicates in the lung for almost two days without inducing an innate immune response. We defined this period between early, undetected virus infection and the first signs of an immune response as the "stealth phase". Our group showed that the NS1 protein of influenza is responsible for the "stealth phase" by hampering cytokine production in vivo. Infection with a virus lacking NS1 triggers an immediate vigorous lung inflammation [96] . Two days after infection with an NS1 competent virus, a robust and abrupt immune response is initiated in the infected lungs. This event demarcates the initiation of innate immunity. The lung innate response includes the production of cytokines (e.g., IL-6, TNF-a, type I IFNs, IFN-γ and IL1-α chemokines (e.g., CCL-2, CCL-20 and KC), the recruitment of diverse cells of the immune system, and the migration of dendritic cells (DCs) to the draining lymph nodes leading to the triggering of T cell responses. This abrupt rise of chemokine is responsible for the recruitment of mononuclear phagocytes, granulocytes and other leukocytes to the site of infection. These recruited cells will play a major role in the eventual clearance of the virus.