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Rabies virus (RABV) transcription and replication take place within viral factories having liquid properties, called Negri bodies (NBs) that are formed by liquid-liquid phase separation (LLPS). The co-expression of RABV nucleoprotein (N) and phosphoprotein (P) in mammalian cells is sufficient to induce the formation of cytoplasmic biocondensates having properties that are like those of NBs. This cellular minimal system was used to identify N and P domains that are essential for biocondensates formation. We also showed that in vitro, in crowded environments, purified P as well as purified N0-P complex (in which N is RNA-free) form liquid condensates of which the properties were characterized. Viral factories are not the only condensates formed in the cell during infection. We also demonstrated that the signaling pathway leading to interferon induction (triggered by RNA viruses infection or detection of dsRNA by innate immunity sensors) proceeds through transient formation of previously unidentified liquid organelles that are targeted by RABV.
Publié le août 31, 2022