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Review
. 2019 Jun:43:101300.
doi: 10.1016/j.smim.2019.101300.

Global virus outbreaks: Interferons as 1st responders

Ben X Wang  1 , Eleanor N Fish  2
Affiliations
Review

Global virus outbreaks: Interferons as 1st responders

Ben X Wang et al. Semin Immunol. 2019 Jun.

Abstract

Outbreaks of severe virus infections with the potential to cause global pandemics are increasing. In many instances these outbreaks have been newly emerging (SARS coronavirus), re-emerging (Ebola virus, Zika virus) or zoonotic (avian influenza H5N1) virus infections. In the absence of a targeted vaccine or a pathogen-specific antiviral, broad-spectrum antivirals would function to limit virus spread. Given the direct antiviral effects of type I interferons (IFNs) in inhibiting the replication of both DNA and RNA viruses at different stages of their replicative cycles, and the effects of type I IFNs on activating immune cell populations to clear virus infections, IFNs-α/β present as ideal candidate broad-spectrum antivirals.

Keywords: Antiviral; Immune response; Interferons-α/β.

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Figures

Fig. 1
Fig. 1
IFNs and their cognate receptors. IFNs are classified based on the receptors through which they signal. Type I IFNs (-α, -β, -δ, -ε, -ζ, -κ, -τ, and -ω) bind to and activate the IFN-α/β receptor (IFNAR) complex. Type II IFN (-γ) activates the IFN-γ receptor 1 and type III IFNs (-λ1, -λ2, -λ3) signal through a receptor complex made up of IL28RA and IL10R2.
Fig. 2
Fig. 2
Pattern Recognition Receptor activation leads to type I IFN production. Binding of PAMPs and DAMPs to host PRRs (TLRs, CLRs, RLRs, NLRs, ALRs, and cGAS) induces signaling cascades that activate IRF3, IRF7 and NF-κB, resulting in the production of type I IFNs-α/β and pro-inflammatory cytokines.
Fig. 3
Fig. 3
Type I IFN signaling. IFNs-α/β bind to IFNAR, inducing the phosphorylation-activation of tyrosine kinases JAK1 and TYK2. JAK1 and TYK2 activation initiates multiple canonical and non-canonical signaling cascades that are critical for the regulation of cellular processes and the expression of ISGs for the innate immune response.
Fig. 4
Fig. 4
Extent of global viral infections. Graphical depiction of global viral outbreaks and summary of the impact of global viral infections based on information gathered from the World Health Organization (WHO) [196]. CHIKV (grey), chikungunya virus; EBOV (red), Ebola virus; IAV (purple), influenza A virus; MERS-CoV (blue), Middle-East respiratory syndrome coronavirus; LASV (pink), Lassa virus; RVFV (blue-purple), Rift Valley fever virus; SARS-CoV (yellow-green), severe acute respiratory syndrome coronavirus; WNV (green), West Nile virus; YFV (brown), yellow fever virus; ZIKV (gold), Zika virus; DENV, dengue virus; HBV, hepatitis B virus; HCV, hepatitis C virus; HIV, human immunodeficiency virus; HPV, human papillomavirus; HSV-1/2, herpes simplex virus type 1/2; PV, poliovirus.
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