A metastable form of the large envelope protein of duck hepatitis B virus:Low-pH release results in a transition to a hydrophobic, potentially fusogenic conformation

We have examined the structure and Fusion potential of the duck hepatitis B virus (DHBV) envelope proteins bg treating subviral particles with deformi ng agents known to release envelope proteins of viruses from a metastable t o a fusion-active state. Exposure of DHBV particles to low pH triggered a m ajor structural change in the large envelope protein (L), resulting in expo sure of trypsin sites within its S domain but without affecting the same re gion in the small surface protein (S) subunits, This conformational change was associated with increased hydrophobicity of the particle surface, most likely arising from surface exposure of the hydrophobic first transmembrane domain (TM1). In the hydrophobic conformation, DHBV particles were able to bind to liposomes and intact cells, while in their absence these particles aggregated, resulting in viral inactivation. These results suggests that s ome L molecules are in a spring-loaded metastable state which, when release d, exposes a prevously hidden hydrophobic domain, a transition potentially representing the fusion-active state of the envelope.