Mechanistic study reveals early endosome hijacking by viral protein 3 in avian birnavirus-infected cells, highlighting a two-stage modular membrane binding mechanism.
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.
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Zanetti et al. (2024) studied this question.
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