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In the developed world,<jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>occurrence has increased as a result of zoonotic transmission from swine. The cellular aspects of<jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>infection, especially the determinants of entry, are poorly understood. In the absence of a robust<jats:italic>in vitro<\/jats:italic>culture system for<jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>, it is not possible to produce high titre infectious virus that can be labeled for tracking its internalization. We have therefore used an<jats:italic>Escherichia coli<\/jats:italic>expressed<jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>\u2010like particle (<jats:styled-content style=\"fixed-case\">HEV\u2010LP<\/jats:styled-content>) to study<jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>entry. Following internalization, the<jats:styled-content style=\"fixed-case\">HEV\u2010LP<\/jats:styled-content>initially trafficks to Rab5\u2010positive compartments<jats:italic>en route<\/jats:italic>to acidic lysosomal compartments where it is degraded. Using pharmacological inhibitors, dominant negative and constitutively active mutants, and<jats:styled-content style=\"fixed-case\">siRNA<\/jats:styled-content>\u2010mediated perturbations, we show that<jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>entry requires dynamin\u20102, clathrin, membrane cholesterol and actin, but is independent of factors associated with macropinocytosis. The<jats:styled-content style=\"fixed-case\">HEV\u2010LP<\/jats:styled-content>results were further validated through infection of liver cells with virus from the stool of an infected patient. The comparative analysis also showed involvement of the phosphatidylinositol\u20103\u2010kinase\/Akt pathway in an early post\u2010entry step of viral replication. This report provides a detailed description of endocytic processes associated with<jats:styled-content style=\"fixed-case\">HEV<\/jats:styled-content>infection.<\/jats:p><jats:p><jats:inline-graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"graphic\/tra12260-gra-0001.png\" xlink:title=\"image\"\/><\/jats:p>","DOI":"10.1111\/tra.12260","type":"journal-article","created":{"date-parts":[[2015,1,23]],"date-time":"2015-01-23T12:03:04Z","timestamp":1422014584000},"page":"398-416","source":"Crossref","is-referenced-by-count":89,"title":["Hepatitis E Virus Enters Liver Cells Through a Dynamin\u20102, Clathrin and Membrane Cholesterol\u2010Dependent Pathway"],"prefix":"10.1111","volume":"16","author":[{"given":"Prasida","family":"Holla","sequence":"first","affiliation":[{"name":"Virology Group, International Centre for Genetic Engineering Biotechnology New Delhi 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