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The immune system's response to viral infections is a complex and coordinated process involving natural killer (NK) cells, T cell-mediated responses, and antibody-mediated responses.
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Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • Interferons and interferon-stimulated genes (ISGs) are crucial for antiviral responses.
  • Interferon stimulated gene 15 (ISG15) is an early and abundant ISG with diverse immune functions.
  • ISG15 acts as a ubiquitin-like modifier (ISGylation) or a secreted cytokine.

Approach:

  • This review synthesizes recent findings on ISG15's role in human antiviral responses.
  • It emphasizes the interplay between ISG15, autophagy, inflammation, and cellular metabolism.
  • Viral strategies to counteract ISG15-mediated immunity are also discussed.

Key Points:

  • ISG15 exhibits context-dependent effects, potentially promoting or hindering immunopathology during infection.
  • Recent human studies contrast with mouse models, highlighting species-specific differences in ISG15 function.
  • Understanding ISG15's role in human antiviral immunity is critical for therapeutic development.

Conclusions:

  • ISG15 is a key regulator of the host antiviral state, influencing multiple cellular pathways.
  • Further research in human models is needed to fully elucidate ISG15's complex functions.
  • Identifying knowledge gaps will guide future studies on ISG15 and viral infections.