An amino acid insertion in the PHI loop of the VP2 capsid protein of serotype 1 infectious bursal disease virus deeply modifies its antigenicity and abrogates its propagation into B cells
摘要
Infectious bursal disease of chickens is an economically important disease induced by infectious bursal disease virus (IBDV). Serotype 1 IBDV strains replicate and destroy chicken B cells in the bursa of Fabricius (BF), a primary lymphoid organ essential for chicken immunity. Using a monoclonal antibody selection process applied to a chicken embryo fibroblast (CEF)-adapted serotype 1 IBDV strain, an escape mutant virus that exhibited an extra Glycine residue inserted at position 323 (PHI loop) of its capsid protein VP2 was isolated. This sole amino acid insertion profoundly modified the antigenicity of the virus, which was then unable to replicate in primary chicken bursal cells. Furthermore, infections of chickens with genetically engineered IBDV strains, derived from either a CEF-adapted or a virulent IBDV strain and bearing the same amino acid insertion, did not result in virus replication in the BF, nor histological lesions of the BF, and induced poor seroconversion. Molecular dynamics analyses on VP2 suggested that this insertion reduces the flexibility of the PHI loop and brings this loop in closer contact with the PBC loop. These changes seem critical for IBDV antigenicity and viral infection in bursal B cells but have a limited impact on IBDV propagation in CEF.