FIG 10.

Models of cellular entry and trafficking of PHEV in Neuro-2a cells. PHEV particles may be transported along actin-rich protrusions to reach the cell surface, and internalization from the plasma membrane may be induced by the classical mechanism of CME. The individual particles are rapidly taken up, internalized into CCVs, and then transported to Rab5-, EEA1-, and NCAM-positive EEs in a clathrin-, dynamin-2-, Eps15-, and Rab5-dependent manner. Through endosome maturation, these virus-containing endosomes acquire Rab7 and become luminal components of Rab7- and Rab9-positive LEs. Further transport to the Golgi apparatus occurs from the late compartments of the endocytic pathway, by an unknown mechanism, and the recycling endosomes are not essential in this process. The vacuolar ATPase (v-ATPase) is responsible for the acidification of the endosomal system, a process that is required for PHEV internalization and the subsequent transport steps. Early and late events in the entry pathway can be blocked by various inhibitors and other perturbants.