A pocket-factor–triggered conformational switch in the hepatitis B virus capsid
Lauriane Lecoq, Shishan Wang, Marie Dujardin, Peter Jan Zimmermann, Leonard Schuster, Marie‐Laure Fogeron, Mathilde Briday, Maarten Schledorn, Thomas Wiegand, Laura Cole, Roland Montserret, Stéphane Bressanelli, Beat H. Meier, Michael Nassal, Anja Böckmann
Abstract
Viral hepatitis is growing into an epidemic illness, and it is urgent to neutralize the main culprit, hepatitis B virus (HBV), a small-enveloped retrotranscribing DNA virus. An intriguing observation in HB virion morphogenesis is that capsids with immature genomes are rarely enveloped and secreted. This prompted, in 1982, the postulate that a regulated conformation switch in the capsid triggers envelopment. Using solid-state NMR, we identified a stable alternative conformation of the capsid. The structural variations focus on the hydrophobic pocket of the core protein, a hot spot in capsid-envelope interactions. This structural switch is triggered by specific, high-affinity binding of a pocket factor. The conformational change induced by the binding is reminiscent of a maturation signal. This leads us to formulate the "synergistic double interaction" hypothesis, which explains the regulation of capsid envelopment and indicates a concept for therapeutic interference with HBV envelopment.