Systems biology unravels interferon responses to respiratory virus infections

Abstract

Interferon production is an important defence against viral replication and its activation is an attractive therapeutic target. However, it has long been known that viruses perpetually evolve a multitude of strategies to evade these host immune responses. In recent years there has been an explosion of information on virus-induced alterations of the host immune response that have resulted from data-rich omics technologies. Unravelling how these systems interact and determining the overall outcome of the host response to viral infection will play an important role in future treatment and vaccine development. In this review we focus primarily on the interferon pathway and its regulation as well as mechanisms by which respiratory RNA viruses interfere with its signalling capacity.

Keywords: Genomics; Innate immunity; Interferon; Proteomics; Respiratory virus; Systems biology.

Figure 1

Interferon activation. NLRX1 : Nucleotide-binding oligomerization domain, leucine rich repeat containing X1; TRIM25: Tripartite motif-containing 25; MITA/STING: Mediator of IRF3 activation/stimulator of interferon genes protein; TRIM11: Tripartite motif containing 11; RNF11: Ring finger protein 11; TRIP: Thyroid receptor-interacting protein; DUBA: Deubiquitinating enzyme A; RLRs: RIG-like receptors; TLRs: Toll-like receptors; IFIT3: Interferon-inducible transmembrane protein 3; MAVS: Mitochondrial anti-viral signaling protein; NLRC5: Nod-like receptor C5; PCBP2: Poly(rC)-binding protein 2; PSMA7: Proteasome subunit alpha type-7; TBK1: Tank binding kinase; IKKe: Inhibitor of nuclear factor kappa-B kinase; IRFs: Interferon regulatory factors; WNT/CTNNB1: Wnt/beta-catenin.