NSs amyloid formation is associated with the virulence of Rift Valley fever virus in mice

Nat Commun. 2020 Jul 1;11(1):3281. doi: 10.1038/s41467-020-17101-y.

Abstract

Amyloid fibrils result from the aggregation of host cell-encoded proteins, many giving rise to specific human illnesses such as Alzheimer's disease. Here we show that the major virulence factor of Rift Valley fever virus, the protein NSs, forms filamentous structures in the brain of mice and affects mortality. NSs assembles into nuclear and cytosolic disulfide bond-dependent fibrillary aggregates in infected cells. NSs structural arrangements exhibit characteristics typical for amyloids, such as an ultrastructure of 12 nm-width fibrils, a strong detergent resistance, and interactions with the amyloid-binding dye Thioflavin-S. The assembly dynamics of viral amyloid-like fibrils can be visualized in real-time. They form spontaneously and grow in an amyloid fashion within 5 hours. Together, our results demonstrate that viruses can encode amyloid-like fibril-forming proteins and have strong implications for future research on amyloid aggregation and toxicity in general.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amyloid / chemistry
  • Amyloid / metabolism*
  • Amyloid / ultrastructure
  • Amyloidogenic Proteins / chemistry
  • Amyloidogenic Proteins / metabolism*
  • Animals
  • Cell Line, Tumor
  • Cell Nucleus / metabolism
  • Cell Nucleus / ultrastructure
  • Cell Nucleus / virology
  • Chlorocebus aethiops
  • HeLa Cells
  • Humans
  • Mice
  • Microscopy, Confocal
  • Microscopy, Electron, Transmission
  • Protein Aggregation, Pathological / metabolism
  • Rift Valley Fever / metabolism*
  • Rift Valley Fever / virology
  • Rift Valley fever virus / metabolism*
  • Rift Valley fever virus / pathogenicity
  • Vero Cells
  • Viral Nonstructural Proteins / chemistry
  • Viral Nonstructural Proteins / metabolism*
  • Virulence
  • Virulence Factors

Substances

  • Amyloid
  • Amyloidogenic Proteins
  • Viral Nonstructural Proteins
  • Virulence Factors