Session topic

17:20–17:25

Title: Glycochenodeoxycholic acid triggers murine Norovirus escape from antibody recognition
ID: PS 18
Type: Poster session
Talk time: 3 + 2 min
Session: Poster session 1
Receptors and entry

Speaker: Stefan Taube (Lübeck/DE)


Abstract - Text

Abstract text (incl. references and figure legends)

Murine norovirus (MNV) is closely related to human norovirus (HuNoV), an infectious agent responsible for acute gastroenteritis worldwide. The icosahedral capsid contains 180 copies of the capsid protein VP1. The main capsid feature is a protruding (P) domain dimer formed by adjacent subunits on the icosahedral surface, while the shell domain forms a tight icosahedral sphere around the single stranded +RNA genome. Bile acids are soluble ligands that act as cofactors contributing to both HuNoV and MNV infectivity. For MNV binding of bile acids to the P domain cause a rotation leading to a collapse of the hinge between shell and protruding domain. The MNV capsid protein also acts as a target for various neutralizing antibodies binding to distal tips of its protruding (P)-domain. Escape mutations in locations distant to antibody binding sites suggested allosteric effects affecting structural plasticity. A specific bile acid, glycochenodeoxycholic acid (GCDCA), was recently shown to induce structural changes in surface-loops and a contraction of the virion. Soluble MNV P domains exist as a mixture of monomers and dimers, with GCDCA shifting the equilibrium towards dimer. Addition of saturating amounts of GCDCA to MNV P‑domains stabilizes the dimer, and removes degrees of freedom of motion, which in turn may entropically assist capsid contraction. Treating MNV virions with GCDCA prior to neutralizing antibody exposure abolishes neutralization. These findings advance our understanding of GCDCA‑induced compaction of MNV capsids and experimentally support an intriguing viral immune escape mechanism relying on GCDCA‑triggered conformational changes of the P‑dimer.