International Journal of Environmental and Biological Sciences Articles Publishing terms and rules Vol. 1 No. 3 (2026): Third Issue - July 2026 2026-07-31

Viral Evasion Mechanisms of Host Interferon Signaling Pathways Viral Evasion and Interferon Signaling

  • Dhefaf Hameed Al-mudhafer
  • Hawraa Ameer Mubark
  • Saif Jabbar Yasir

01Abstract

       Interferons (IFNs) are one of the core pillars of innate antiviral immunity that together forms a cascade in signaling network by intra- and inter-cellular responses, detecting viral infection, activating Janus kinase-signal transducer and activator of transcription (JAK–STAT), and ultimately inducing hundreds of interferon-stimulated genes (ISGs) which inhibit viral propagation. Nonetheless, viruses have developed intricate immune evasion strategies that target virtually all facets of the interferon response thus promoting viral survival, persistence, and pathogenesis. This review summarizes the basic molecular mechanisms of host interferon signaling and the various viruses that have evolved to counteract these pathways. Most notably with respect to viral interference with pattern recognition receptor signaling, type I interferon induction, JAK STAT signal transduction and ISGF3 complex formation and host restriction factors. Soon afterward, the review introduces how viruses manipulate post-translational modifications (PTMs), such as ubiquitination, ISGylation, SUMOylation and proteasomal degradation to potentiate their effects on innate immune responses. The coevolution between virus and host is emphasized as a key mechanism promoting viral immune antagonists in one hand and host antiviral restriction factors on the other, contributing to rapid diversification of both sectors. Finally, novel therapeutic approaches targeting the restoration of interferon signaling via host-directed therapies, inhibition of viral antagonists, modulation of pathways responsible for


post-translational modifications (PTMs) and personalized immunotherapies are thoroughly discussed. Targeting host–virus interaction networks rather than viral replication alone provide new avenues for broad-spectrum antiviral therapies, which are less susceptible to resistance due to the dynamic nature of host and virus evolution. Such integration of structural biology, systems immunology, multi-omics technologies with clinical investigation will be necessary for translating mechanistic insights into therapeutics against viral pathogens and enhancing preparedness to future viral threats.

Keywords Interferon signaling Type I interferon JAK–STAT pathway Viral immune evasion Interferon-stimulated genes (ISGs) Pattern recognition receptors (PRRs) ISGylation Innate antiviral immunity Host-directed antiviral therapy

02Authors

Dhefaf Hameed Al-mudhafer
Department of Medical Microbiology, College of Medicine, University of Kufa, Najaf, Iraq
Hawraa Ameer Mubark
Department of Medical Microbiology, College of Medicine, University of Kufa, Najaf, Iraq.
Saif Jabbar Yasir
Department of Medical Microbiology, College of Medicine, University of Kufa, Najaf, Iraq

03Article Details

Section
Articles Publishing terms and rules
Pages
148-204
Published
2026-07-31

How to Cite

Viral Evasion Mechanisms of Host Interferon Signaling Pathways: Viral Evasion and Interferon Signaling . (2026). International Journal of Environmental and Biological Sciences, 1(3), 148-204. https://doi.org/10.63939/1ctxw017

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