Like a prion, a virus that causes amyloid plaques

While amyloid fibril aggregates are known to cause numerous diseases such as Alzheimer’s disease, Creutzfeldt-Jakob disease, and Parkinson’s disease, researchers have now shown for the first time that a virus may be the source of these harmful accumulations. Until now, only prions were thought to be capable of transmitting this type of disease. The accumulation of proteins in the brain and localized or systemic tissue deposits of amyloid fibrils are the cause of many diseases in humans and animals. These aggregates result from the misfolding and aberrant assembly of proteins into linear, ordered fibrils. To date, approximately 50 human proteins have been identified as involved in the formation of these amyloid fibrils, many of which cause diseases such as Alzheimer’s disease, Parkinson’s disease, and Creutzfeldt-Jakob disease. However, although the formation and accumulation of amyloid deposits are clearly associated with protein misfolding diseases (PDMs), the exact molecular and cellular mechanisms remain unclear. Normally, these diseases occur spontaneously or, to a lesser extent, are inherited. Until now, only prion-related PDMs were transmissible. However, research on the Rift Valley fever virus (RVFV) is overturning this paradigm. RVFV, which infects humans and ruminants in Africa through mosquito bites and can be fatal, is also capable of forming clusters resembling amyloid fibrils in the brain. And a team of researchers from INRAE, in partnership with the Pasteur Institute, the University of Heidelberg, and the German Cancer Research Center, has discovered that the main virulence factor of RFV, the NS protein, forms filamentous structures in the brains of mice and accelerates mortality. Produced in infected cells, NS proteins form large aggregates structurally similar to amyloid fibrils. The assembly of viral fibrils can be visualized in real time. This spontaneous transformation occurs very quickly, taking about 5 hours on average. In an infectious context, these fibrils are critical to the virus’s ability to evade the immune response and are likely responsible for VFVR’s virulence. Like prions, NS is therefore capable of forming amyloid-like fibrils. This is the first time a viral protein has been identified as responsible for the formation of amyloid fibrils. This is a significant discovery that advances our understanding of VFVR, which poses a real challenge for African nations. .