Fig. 6: GII.4 uses a complex entry mechanism involving cellular wound repair mechanisms and CLIC-mediated endocytosis.
From: CLIC and membrane wound repair pathways enable pandemic norovirus entry and infection
(1) Binding of GII.4 with its glycan receptor (HBGAs and possibly with a still unidentified co-receptor) on the cell surface (2) induces plasma membrane wounding (3) triggering signaling responses that direct multiple membrane repair cellular components to the injury site. (4) ASM translocation to the plasma membrane surface results in conversion of sphingomyelin (SM) to ceramide. (5) Ceramide formation along with other membrane repair processes involving gal-3 (glycan damage sensor), ALIX (Ca2+ sensor) and membrane recycling processes regulated by Rab11 and Rab14 result in membrane reorganization and receptor clustering leading to (6) tubular carrier formation due to multiple interactions of virus with host factors causing membrane bending and (7) endocytosis regulated by Cdc42 and cholesterol. (8) GII.4 entry into the cell results in V-ATPase regulated endosomal acidification causing (9) conformational changes in the virus capsid and release of the viral genome from the endosomal compartment.
