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

Clement, Christian; Tiwari, Vaibhav; Scanlan, Perry M.; Valyi-Nagy, Tibor; Yue, Beatrice Y. J. T.; Shukla, Deepak

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 non-professional phagocytes.

HERPESVIRUSES; CELLS; ENDOCYTOSIS; PHAGOCYTOSIS; COATED vesicles

Journal of Cell Biology, 2006, Vol 174, Issue 7, p1009

0021-9525

Academic Journal

10.1083/jcb.200509155