A novel role for phagocytosis-like uptake in herpes simplex virus entry |
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Authors: | Clement Christian Tiwari Vaibhav Scanlan Perry M Valyi-Nagy Tibor Yue Beatrice Y J T Shukla Deepak |
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Institution: | Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, College of Medicine, Chicago, IL 60612, USA. |
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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. |
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