The Innate Antiviral Response in Animals: An Evolutionary Perspective from Flagellates to Humans

Viruses. 2019 Aug 16;11(8):758. doi: 10.3390/v11080758.


Animal cells have evolved dedicated molecular systems for sensing and delivering a coordinated response to viral threats. Our understanding of these pathways is almost entirely defined by studies in humans or model organisms like mice, fruit flies and worms. However, new genomic and functional data from organisms such as sponges, anemones and mollusks are helping redefine our understanding of these immune systems and their evolution. In this review, we will discuss our current knowledge of the innate immune pathways involved in sensing, signaling and inducing genes to counter viral infections in vertebrate animals. We will then focus on some central conserved players of this response including Toll-like receptors (TLRs), RIG-I-like receptors (RLRs) and cGAS-STING, attempting to put their evolution into perspective. To conclude, we will reflect on the arms race that exists between viruses and their animal hosts, illustrated by the dynamic evolution and diversification of innate immune pathways. These concepts are not only important to understand virus-host interactions in general but may also be relevant for the development of novel curative approaches against human disease.

Keywords: RLR; STING; TLR; animals; cGAS; evolution; innate immunity; viral sensing.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Biological Evolution*
  • DEAD Box Protein 58 / genetics
  • DEAD Box Protein 58 / immunology
  • Humans
  • Immunity, Innate*
  • Toll-Like Receptors / genetics
  • Toll-Like Receptors / immunology
  • Virus Diseases / genetics
  • Virus Diseases / immunology*
  • Virus Physiological Phenomena
  • Viruses / genetics


  • Toll-Like Receptors
  • DEAD Box Protein 58