Story of Rhabdoviridae phosphoprotein

Orateur : Francine GERARD BARAGGIA (ATER Grenoble-INP Phelma / LMGP)

Vesicular stomatitis virus (Vesiculovirus, VSV) and rabies virus (Lyssavirus, RabV) belong to the Rhabdoviridae family. VSV serves as a model for studying the multiplication of viruses from the Mononegavirales order, whereas rabies is still a serious health problem in developing countries where it kills more than 50 000 people per year. The genome of these viruses is composed of one single stranded RNA molecule of negative polarity, and encodes five proteins. The nucleoprotein (N) binds to the viral genome forming an N-RNA complex that is packaged into virions that serves as a matrix for viral transcription and replication. The phosphoprotein (P) is a cofactor of the viral RNA-dependant RNA polymerase (L), and a chaperone of the nucleoprotein. The C-terminal domain of P binds to the N-RNA matrix and its N-terminal domain binds to the polymerase, making a physical link between the viral genome and the polymerase. The stoichiometry, the structure and the exact functions of P oligomers were controversial or unknown. In this presentation, I will present the biophysical and structural characterization studies I have made of the Rhabdoviridae phosphoprotein and of the complexes that it forms with N-RNA, N in its soluble form (named N°), and with component of the cell host. Our results showed that P is a modular protein with intrinsically disordered regions and folded domains that play specific and similar roles in the replication of different viruses, and in some cases, hijacks cell components to the virus advantage and is involved in immune evasion. All together, these studies provide keys to understand the dynamic of the replicative complex of these viruses.

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