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Birnaviral Hijacking of Endosomal Membranes

2024; eLife Sciences Publications Ltd; Volume: 13; Linguagem: Inglês

10.7554/elife.97261

2050-084X

Flavia Zanetti, I. Fernández, Eduard Baquero, Pablo Guardado‐Calvo, Andres Ferrino-Iriarte, Sarah Dubois, Étienne Morel, Victoria Alfonso, Milton Osmar Aguilera, María E Celayes, Luis Mariano Polo, Laila Suhaiman, Vanesa V Galassi, María V. Chiarpotti, Carolina Allende-Ballestero, Javier M. Rodrı́guez, José R. Castón, Diego Lijavetzky, Oscar Taboga, Marı́a I. Colombo, Mario G. Del Pópolo, F.A. Rey, Laura Ruth Delgui,

Plant Virus Research Studies

Birnaviruses form a distinct class of double-stranded RNA (dsRNA) viruses characterized by the absence of a transcription-competent inner core particle. The early endosomes (EE) of cells infected with the infectious bursal disease virus (IBDV) - a prototypical birnavirus and an important avian pathogen - constitute a platform for viral replication. Here, we study the mechanism of birnaviral hijacking of EE membranes for this process. We demonstrate that the viral protein 3 (VP3) specifically binds to phosphatidylinositol-3-phosphate (PI3P) present in EE membranes. We identify the domain of VP3 involved in PI3P-binding and its role in viral replication. Finally, our molecular simulations results unveil a two-stage modular mechanism for VP3 association with EE. Firstly, the carboxy-terminal region of VP3 adsorbs to the membrane via non-specific electrostatic interactions. Then, in the second stage, the VP3 core seals the membrane engagement by specifically binding PI3P through its P2 domain, additionally promoting PI3P accumulation.