A novel role for phagocytosis-like uptake in herpes simplex virus entry.
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.
Clement
Christian
C
Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, College of Medicine, Chicago, IL 60612, USA.
Tiwari
Vaibhav
V
Scanlan
Perry M
PM
Valyi-Nagy
Tibor
T
Yue
Beatrice Y J T
BY
Shukla
Deepak
D
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
D000199:Actins; D011991:Receptors, Virus; D020742:rhoA GTP-Binding Protein