On the role of VP3-PI3P interaction in birnavirus endosomal membrane targeting
Birnaviruses are a group of double-stranded RNA (dsRNA) viruses infecting birds, fish, and insects. Early endosomes (EE) constitute the platform for viral replication. Here, we study the mechanism of birnaviral targeting of EE membranes. Using the Infectious Bursal Disease Virus (IBDV) as a model, we validate that the viral protein 3 (VP3) binds to phosphatidylinositol-3-phosphate (PI3P) present in EE membranes. We identify the domain of VP3 involved in PI3P-binding, named P2 and localized in the core of VP3, and establish the critical role of the arginine at position 200 (R 200 ), conserved among all known birnaviruses. Mutating R 200 abolishes viral replication. Moreover, we propose a two-stage modular mechanism for VP3 association with EE. Firstly, the carboxy-terminal region of VP3 adsorbs on the membrane, and then the VP3 core reinforces the membrane engagement by specifically binding PI3P through its P2 domain, additionally promoting PI3P accumulation.
Authors
- José R. Castón (ORCID: https://orcid.org/0000-0003-2350-9048)
- Flavia Zanetti (ORCID: https://orcid.org/0000-0002-4337-4163)
- Pablo Guardado‐Calvo (ORCID: https://orcid.org/0000-0001-7292-5270)
- Javier M. Rodrı́guez (ORCID: https://orcid.org/0000-0003-0146-9903)
- Marı́a I. Colombo (ORCID: https://orcid.org/0000-0002-2676-3845)
- Carolina Allende-Ballestero
- Sarah Dubois (ORCID: https://orcid.org/0009-0000-7504-7135)
- María V. Chiarpotti (ORCID: https://orcid.org/0000-0003-2480-0494)
- Eduard Baquero (ORCID: https://orcid.org/0000-0002-4701-4181)
- F.A. Rey (ORCID: https://orcid.org/0000-0002-9953-7988)
- Oscar Taboga
- Milton Osmar Aguilera (ORCID: https://orcid.org/0000-0002-5413-769X)
- Luis Mariano Polo (ORCID: https://orcid.org/0000-0001-9257-6127)
- Laura Ruth Delgui (ORCID: https://orcid.org/0000-0002-3647-3593)
- Mario G. Del Pópolo (ORCID: https://orcid.org/0000-0002-1435-2424)
- Diego Lijavetzky (ORCID: https://orcid.org/0000-0003-4207-3067)
- Victoria Alfonso (ORCID: https://orcid.org/0000-0002-9167-6107)
- Étienne Morel (ORCID: https://orcid.org/0000-0002-4763-4954)
- I. Fernández (ORCID: https://orcid.org/0000-0003-2632-8111)
- Laila Suhaiman (ORCID: https://orcid.org/0000-0001-8376-2673)
- Vanesa V Galassi (ORCID: https://orcid.org/0000-0002-8058-6069)
- María E Celayes (ORCID: https://orcid.org/0009-0005-6905-6218)
- Andres Ferrino-Iriarte (ORCID: https://orcid.org/0000-0003-0821-556X)
Institutions
- Centre National de la Recherche Scientifique (FR)
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- Inserm (FR)
- Institut Pasteur (FR)
- Universidad Nacional de Cuyo (AR)
- Université Paris Cité (FR)
- Institut Necker Enfants Malades (FR)
- Instituto Interdisciplinario de Ciencias Básicas (AR)
- Instituto de Biología Agrícola de Mendoza (AR)
- Instituto de Histología y Embriología de Mendoza (AR)
- Instituto de Agrobiotecnología del Litoral (AR)
- National Agricultural Technology Institute (AR)
- Hospital César Milstein (AR)
Publication Details
- Journal
- eLife
- Published
- 2025-03-06
- DOI
- https://doi.org/10.7554/elife.97261.3
- Primary Topic
- Virology and Viral Diseases
- Type
- article
- Field-Weighted Citation Impact
- 0.00
Funders
- Comunidad de Madrid
- International Union of Biochemistry and Molecular Biology
- Consejo Nacional de Investigaciones Científicas y Técnicas
- Ministerio de Ciencia e Innovación
- Universidad Nacional de Cuyo