Structure, interactions with host cell and functions of rhabdovirus phosphoprotein

• Published in: Future Virology Vol. 6; no. 4; pp. 465 - 481
• Main Authors: Leyrat, Céédric, Ribeiro, Euripedes A, Géérard, Francine CA, Ivanov, Ivan, Ruigrok, Rob WH, Jamin, Marc
• Format: Journal Article Book Review
• Language: English
• Published: London Future Medicine Ltd 01.04.2011
• Subjects: Anopheles; Binding sites; Biological response modifiers; Chaperones; Cofactors; Cytoskeleton; Genetic aspects; Genomes; Health aspects; Immune response; Interferon; intrinsically disordered region; Nucleoproteins; phosphoprotein; Phosphoproteins; Proteins; Rabies; Rabies virus; Replication; Rhabdovirus; RNA; RNA polymerase; RNA viruses; Transcription; virus; Viruses
• ISSN: 1746-0794; 1746-0808
• DOI: 10.2217/fvl.11.10

Rabies is an incurable albeit preventable disease that remains an important human health issue, with the number of deaths exceeding 50,000 people each year. Its causative agent, the rabies virus, is a negative-sense RNA virus, the genome of which encodes five proteins. Three of these proteins, the nucleoprotein, the phosphoprotein (P) and the large protein, are required to synthesize viral RNA in an efficient and regulated manner. P plays multiple roles during the transcription and replication of the RNA genome. It acts as a noncatalytic cofactor of the large protein polymerase and it chaperones nucleoprotein. Recent structural characterizations of rabies virus P revealed that P forms elongated and flexible dimers and uncovered the structural basis of its modular organization, revealing the existence of two independent structured domains and two long intrinsically disordered regions. In addition, recent studies also revealed that P interacts with nucleocytoplasmic trafficking carriers and with the host cell cytoskeleton, probably allowing viral components to be transported within the host cell and blocking the innate immune response by inhibiting different steps of the interferon pathway. With multiple binding sites for different viral and cellular partners located in either its structured or disordered regions, P appears to be a flexible '‘hub ’ protein that connects viral or cellular proteins and allows their assembly into multimolecular complexes. These new findings shed light on the mechanism of replication of the virus and on the intimate interactions between the virus and its host cell, and will also help to identify new targets for the development of antiviral treatments.