On the role of VP3-PI3P interaction in birnavirus endosomal membrane targeting.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40047543.
- Also identified by DOI 10.7554/eLife.97261 and PMC identifier 11884790.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
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<sub>200</sub>), conserved among all known birnaviruses. Mutating R<sub>200</sub> 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.
Medical subject headings
- Endosomes
- Phosphatidylinositol Phosphates
- Viral Structural Proteins
- Infectious bursal disease virus
- Intracellular Membranes