Suppression of Innate Immunity by Orthomyxoviruses

This chapter discusses how influenza virus infection triggers the production of type I interferon (IFNs), the signaling cascades that the cytokines stimulate to establish a protective antiviral response, and the mechanisms that orthomyxoviruses employ to circumvent the host’s innate immunity. Orthomyxoviruses employ several strategies to circumvent the host’s innate and adaptive immune responses; the effectiveness by which the viruses apply the strategies contributes to the clinical outcome of virus infections. For influenza A viruses, the viral hemagglutinin and neuraminidase glycoproteins substantially contribute to the pathogenesis of influenza virus infections. An important consideration in the induction of IFN by influenza virus relates to the actual nature of the viral inducer recognized by the cellular sensors. IFN-inducible Mx homologues belong to the dynamin-like family of GTPases that are normally associated with intracellular vesicle trafficking and organelle homeostasis. Promyelocytic leukemia (PML) protein (also known as TRIM19) is an additional IFN-inducible protein that accumulates within nuclear structures that have been referred to as nuclear dot 10 (ND10) or nuclear bodies. The studies discussed in the chapter have concisely described the mechanisms by which, in the absence of the nonstructural protein 1 (NS1), the host detects virus replication, stimulates expression of the IFN-β gene and IFN-stimulated genes (ISGs), and establishes an antiviral state that controls replication of and pathogenicity resulting from infection by orthomyxoviruses.