title: A novel role for phagocytosis-like uptake in herpes simplex virus entry.
abstract: It is becoming increasingly clear that herpesviruses can exploit the endocytic pathway to infect cells, yet several important features of this process remain poorly defined. Using herpes simplex virus-1 (HSV-1) as a model, we demonstrate that endocytosis of the virions mimic many features of phagocytosis. During entry, HSV-1 virions associated with plasma membrane protrusions followed by a phagocytosis-like uptake involving rearrangement of actin cytoskeleton and trafficking of the virions in large phagosome-like vesicles. RhoA GTPase was activated during this process and the mode of entry was cell type-specific. Clathrin-coated vesicles had no detectable role in virion trafficking as Eps15 dominant-negative mutants failed to affect HSV-1 uptake. Binding and fusion of the virion envelope with the phagosomal membrane is likely facilitated by clustering of nectin-1 (or HVEM) in phagosomes, which was observed in infected cells. Collectively, our data suggests a novel mode of uptake by which the virus can infect both professional and nonprofessional phagocytes.
authors.affiliation: Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, College of Medicine, Chicago, IL 60612, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Clement
authors.forename: Vaibhav
authors.initials: V
authors.lastname: Tiwari
authors.forename: Perry M
authors.initials: PM
authors.lastname: Scanlan
authors.forename: Tibor
authors.initials: T
authors.lastname: Valyi-Nagy
authors.forename: Beatrice Y J T
authors.initials: BY
authors.lastname: Yue
authors.forename: Deepak
authors.initials: D
authors.lastname: Shukla
mesh_terms: D000199:Actins / Q000502:physiology; D000818:Animals; D016466:CHO Cells; D021961:Cell Membrane Structures / Q000737:chemistry / Q000648:ultrastructure / Q000821:virology; D002478:Cells, Cultured; D022163:Clathrin-Coated Vesicles / Q000737:chemistry; D003315:Cornea / Q000166:cytology / Q000821:virology; D006224:Cricetinae; D005347:Fibroblasts / Q000648:ultrastructure / Q000821:virology; D018259:Herpesvirus 1, Human / Q000502:physiology* / Q000648:ultrastructure; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008954:Models, Biological; D010587:Phagocytosis; D011940:Receptor Aggregation; D011991:Receptors, Virus / Q000502:physiology*; D015398:Signal Transduction; D020742:rhoA GTP-Binding Protein / Q000502:physiology
chemical_list: D000199:Actins; D011991:Receptors, Virus; D020742:rhoA GTP-Binding Protein