FIG 6.
Proposed mechanism of CAR-mediated CAV-2 entry in fibroblast-like cells. This scheme recapitulates CAR-mediated endocytosis upon FKCAV and CAV-2 engagement (14). CAR is located in lipid rafts (lipid bilayer in brown).The trimeric FKCAV binds with high affinity to D1 and triggers CAR endocytosis, which requires lipid raft integrity, dynamin, and actin, leading to targeting to endolysosomes for degradation. CARΔICD is not internalized upon FKCAV binding (black cross). CARFL is coendocytosed with CAV-2 and reaches transferrin-positive endosomal structures within 30 min and Rab7+ structures in the late stage of endocytosis prior to endosomal escape. Virions further traffic via microtubules to reach the MTOC. CARΔICD is poorly cointernalized with CAV-2 and triggers delay in CAV-2 trafficking in each step, which ultimately impacts vector transduction. The absence of the CAR ICD does not impact HAdV-C5 and HAdV-C5ΔRGD cell transduction (far right), highlighting different uses of CAR among AdV types.