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

CiteULike
Complore
Connotea
Del.icio.us
Digg
Facebook
Reddit
Technorati
Twitter What's this?
This article has been cited by other articles:
-
O'Donnell, C. D., Shukla, D.
(2009). A Novel Function of Heparan Sulfate in the Regulation of Cell-Cell Fusion. J. Biol. Chem.
284: 29654-29665
[Abstract]
[Full Text]
-
Petermann, P., Haase, I., Knebel-Morsdorf, D.
(2009). Impact of Rac1 and Cdc42 Signaling during Early Herpes Simplex Virus Type 1 Infection of Keratinocytes. J. Virol.
83: 9759-9772
[Abstract]
[Full Text]
-
Miller, M. S., Hertel, L.
(2009). Onset of Human Cytomegalovirus Replication in Fibroblasts Requires the Presence of an Intact Vimentin Cytoskeleton. J. Virol.
83: 7015-7028
[Abstract]
[Full Text]
-
Clement, C., Bhattacharjee, P. S., Kaufman, H. E., Hill, J. M.
(2009). Heat-Induced Reactivation of HSV-1 in Latent Mice: Upregulation in the TG of CD83 and Other Immune Response Genes and Their LAT-ICP0 Locus. IOVS
50: 2855-2861
[Abstract]
[Full Text]
-
Neuhierl, B., Feederle, R., Adhikary, D., Hub, B., Geletneky, K., Mautner, J., Delecluse, H.-J.
(2009). Primary B-Cell Infection with a {Delta}BALF4 Epstein-Barr Virus Comes to a Halt in the Endosomal Compartment yet Still Elicits a Potent CD4-Positive Cytotoxic T-Cell Response. J. Virol.
83: 4616-4623
[Abstract]
[Full Text]
-
Lyman, M. G., Enquist, L. W.
(2009). Herpesvirus Interactions with the Host Cytoskeleton. J. Virol.
83: 2058-2066
[Full Text]
-
Akhtar, J., Tiwari, V., Oh, M.-J., Kovacs, M., Jani, A., Kovacs, S. K., Valyi-Nagy, T., Shukla, D.
(2008). HVEM and Nectin-1 Are the Major Mediators of Herpes Simplex Virus 1 (HSV-1) Entry into Human Conjunctival Epithelium. IOVS
49: 4026-4035
[Abstract]
[Full Text]
-
Maurer, U. E., Sodeik, B., Grunewald, K.
(2008). Native 3D intermediates of membrane fusion in herpes simplex virus 1 entry. Proc. Natl. Acad. Sci. USA
105: 10559-10564
[Abstract]
[Full Text]
-
Gillet, L., Colaco, S., Stevenson, P. G.
(2008). Glycoprotein B switches conformation during murid herpesvirus 4 entry. J. Gen. Virol.
89: 1352-1363
[Abstract]
[Full Text]
-
Dupuy, A. G., Caron, E.
(2008). Integrin-dependent phagocytosis - spreading from microadhesion to new concepts. J. Cell Sci.
121: 1773-1783
[Abstract]
[Full Text]
-
Delboy, M. G., Roller, D. G., Nicola, A. V.
(2008). Cellular Proteasome Activity Facilitates Herpes Simplex Virus Entry at a Postpenetration Step. J. Virol.
82: 3381-3390
[Abstract]
[Full Text]
-
Nagel, C.-H., Dohner, K., Fathollahy, M., Strive, T., Borst, E. M., Messerle, M., Sodeik, B.
(2008). Nuclear Egress and Envelopment of Herpes Simplex Virus Capsids Analyzed with Dual-Color Fluorescence HSV1(17+). J. Virol.
82: 3109-3124
[Abstract]
[Full Text]
-
Frampton, A. R. Jr., Stolz, D. B., Uchida, H., Goins, W. F., Cohen, J. B., Glorioso, J. C.
(2007). Equine Herpesvirus 1 Enters Cells by Two Different Pathways, and Infection Requires the Activation of the Cellular Kinase ROCK1. J. Virol.
81: 10879-10889
[Abstract]
[Full Text]
-
Wang, C. Q.F., Cheng, C. Y.
(2007). A seamless trespass: germ cell migration across the seminiferous epithelium during spermatogenesis. JCB
178: 549-556
[Abstract]
[Full Text]
-
Tiwari, V., Shukla, S. Y., Yue, B. Y. J. T., Shukla, D.
(2007). Herpes simplex virus type 2 entry into cultured human corneal fibroblasts is mediated by herpesvirus entry mediator. J. Gen. Virol.
88: 2106-2110
[Abstract]
[Full Text]
-
Hambleton, S., Steinberg, S. P., Gershon, M. D., Gershon, A. A.
(2007). Cholesterol Dependence of Varicella-Zoster Virion Entry into Target Cells. J. Virol.
81: 7548-7558
[Abstract]
[Full Text]
-
Tiwari, V., O'Donnell, C., Copeland, R. J., Scarlett, T., Liu, J., Shukla, D.
(2007). Soluble 3-O-sulfated heparan sulfate can trigger herpes simplex virus type 1 entry into resistant Chinese hamster ovary (CHO-K1) cells. J. Gen. Virol.
88: 1075-1079
[Abstract]
[Full Text]
-
Subramanian, R. P., Geraghty, R. J.
(2007). Herpes simplex virus type 1 mediates fusion through a hemifusion intermediate by sequential activity of glycoproteins D, H, L, and B. Proc. Natl. Acad. Sci. USA
104: 2903-2908
[Abstract]
[Full Text]
-
Clement, C., Tiwari, V., Scanlan, P. M., Valyi-Nagy, T., Yue, B. Y.J.T., Shukla, D.
(2006). A novel role for phagocytosis-like uptake in herpes simplex virus entry. JEM
203: i25-25
[Full Text]