Mechanisms and therapeutic potential of interactions between human amyloids and viruses

Cell Mol Life Sci. 2021 Mar;78(6):2485-2501. doi: 10.1007/s00018-020-03711-8. Epub 2020 Nov 26.


The aggregation of specific proteins and their amyloid deposition in affected tissue in disease has been studied for decades assuming a sole pathogenic role of amyloids. It is now clear that amyloids can also encode important cellular functions, one of which involves the interaction potential of amyloids with microbial pathogens, including viruses. Human expressed amyloids have been shown to act both as innate restriction molecules against viruses as well as promoting agents for viral infectivity. The underlying molecular driving forces of such amyloid-virus interactions are not completely understood. Starting from the well-described molecular mechanisms underlying amyloid formation, we here summarize three non-mutually exclusive hypotheses that have been proposed to drive amyloid-virus interactions. Viruses can indirectly drive amyloid depositions by affecting upstream molecular pathways or induce amyloid formation by a direct interaction with the viral surface or specific viral proteins. Finally, we highlight the potential of therapeutic interventions using the sequence specificity of amyloid interactions to drive viral interference.

Keywords: Antiviral; Protein aggregation; Seeding; Surface-catalyzed nucleation.

Publication types

  • Review

MeSH terms

  • Alzheimer Disease / metabolism
  • Alzheimer Disease / pathology
  • Alzheimer Disease / virology
  • Amyloid / metabolism*
  • Amyloid beta-Peptides / metabolism
  • HIV / physiology
  • Herpesviridae / physiology
  • Humans
  • Orthomyxoviridae / physiology
  • Viruses / metabolism*
  • tau Proteins / metabolism


  • Amyloid
  • Amyloid beta-Peptides
  • tau Proteins