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.
Highlights
Amyloid fibrils result from the aggregation of host cell-encoded proteins, many giving rise to specific human illnesses such as Alzheimer’s disease
Cells were exposed to the wt virus and analyzed by confocal microscopy after immunofluorescence staining against NSs
We expanded the concept of amyloid fibrils to authentic viral infections
Summary
Amyloid fibrils result from the aggregation of host cell-encoded proteins, many giving rise to specific human illnesses such as Alzheimer’s disease. Amyloid-type aggregates result from the misfolding and aberrant assembly of amyloidogenic proteins into highly ordered, linear fibrils[1] In this process, a partially unfolded monomeric precursor adopts an alternative β-sheet-rich conformation, which is distinct from its soluble native state. Amyloid deposits that are formed in tissues and cells are highly heterogeneous in size and shape but are usually present in the detergent-insoluble fraction after lysis In ultrastructure studies they are typically composed of many fibrils that often appear nonbranched, straight, or helical, with a diameter in the range of 10 nm and a length of up to several micrometers[1,3]. Though truncated forms of genetically engineered viral proteins were shown to exhibit some amyloid characteristics in vitro[5,6], no virus-encoded amyloid-like fibrils have yet been described in vivo, i.e., in authentic viral infections in cell model systems or animals and without any genetic or chemical modifications
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