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Published 25 September 2006. doi:10.1083/jcb.200509155
The Rockefeller University Press, 0021-9525 $8.00
JCB, Volume 174, Number 7, 1009-1021
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Article

A novel role for phagocytosis-like uptake in herpes simplex virus entry

Christian Clement1,2, Vaibhav Tiwari1, Perry M. Scanlan1,2, Tibor Valyi-Nagy3, Beatrice Y.J.T. Yue1, and Deepak Shukla1,2

1 Department of Ophthalmology and Visual Sciences, 2 Department of Microbiology and Immunology, and 3 Department of Pathology University of Illinois at Chicago, College of Medicine, Chicago, IL 60612

Correspondence to Deepak Shukla: dshukla{at}uic.edu

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.

C. Clement and V. Tiwari contributed equally to this work.

Abbreviations used in this paper: CHO, Chinese hamster ovary; CF, corneal fibroblasts; CM, confocal microscopy; Cyto D, cytochalasin D; EEA1, early endosome antigen 1; HS, heparan sulfate; HSK, herpetic stromal keratitis; HSPG, heparan sulfate proteoglycans; HSV-1, herpes simplex virus-1; Lat B, latrunculin B; nectin-1-EGFP, nectin-1 with enhanced green fluorescent protein; TM, trabecular meshwork; TEM, transmission electron microscopy; SEM, scanning electron microscopy.


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