Nonprofessional Phagocytosis Can Facilitate Herpesvirus Entry into Ocular Cells

Phagocytosis is a major mechanism by which the mediators of innate immunity thwart microbial infections. Here we demonstrate that human herpesviruses may have evolved a common mechanism to exploit a phagocytosis-like entrapment to gain entry into ocular cells. While herpes simplex virus-1 (HSV-1) ca...

Full description

Bibliographic Details
Main Authors: Vaibhav Tiwari, Deepak Shukla
Format: Article
Language:English
Published: Hindawi Limited 2012-01-01
Series:Clinical and Developmental Immunology
Online Access:http://dx.doi.org/10.1155/2012/651691
id doaj-c0236fde4e7c47ce8f6adedc686783d0
record_format Article
spelling doaj-c0236fde4e7c47ce8f6adedc686783d02020-11-24T23:48:48ZengHindawi LimitedClinical and Developmental Immunology1740-25221740-25302012-01-01201210.1155/2012/651691651691Nonprofessional Phagocytosis Can Facilitate Herpesvirus Entry into Ocular CellsVaibhav Tiwari0Deepak Shukla1Department of Microbiology and Immunology, Midwestern University, Downers Grove, IL 60515, USADepartment of Microbiology and Immunology, University of Illinois at Chicago, 1855 W. Taylor Street, LIERI Building, Chicago, IL 60612, USAPhagocytosis is a major mechanism by which the mediators of innate immunity thwart microbial infections. Here we demonstrate that human herpesviruses may have evolved a common mechanism to exploit a phagocytosis-like entrapment to gain entry into ocular cells. While herpes simplex virus-1 (HSV-1) causes corneal keratitis, cytomegalovirus (CMV) is associated with retinitis in immunocompromised individuals. A third herpesvirus, human herpesvirus-8 (HHV-8), is crucial for the pathogenesis of Kaposi’s sarcoma, a common AIDS-related tumor of eyelid and conjunctiva. Using laser scanning confocal microscopy, we show that successful infection of ocular cell types by all the three viruses, belonging to three divergent subfamilies of herpesviruses, is facilitated by induction of F-actin rich membrane protrusions. Inhibitors of F-actin polymerization and membrane protrusion formation, cytochalasin D and latrunculin B, were able to block infection by all three viruses. Similar inhibition was seen by blocking phosphoinositide 3 kinase signaling, which is required for microbial phagocytosis. Transmission electron microscopy data using human corneal fibroblasts for HSV-1, human retinal pigment epithelial cells for CMV, and human conjunctival epithelial cells for HHV-8 are consistent with the possibility that pseudopod-like membrane protrusions facilitate virus uptake by the ocular cells. Our findings suggest a novel mechanism by which the nonprofessional mediators of phagocytosis can be infected by human herpesviruses.http://dx.doi.org/10.1155/2012/651691
collection DOAJ
language English
format Article
sources DOAJ
author Vaibhav Tiwari
Deepak Shukla
spellingShingle Vaibhav Tiwari
Deepak Shukla
Nonprofessional Phagocytosis Can Facilitate Herpesvirus Entry into Ocular Cells
Clinical and Developmental Immunology
author_facet Vaibhav Tiwari
Deepak Shukla
author_sort Vaibhav Tiwari
title Nonprofessional Phagocytosis Can Facilitate Herpesvirus Entry into Ocular Cells
title_short Nonprofessional Phagocytosis Can Facilitate Herpesvirus Entry into Ocular Cells
title_full Nonprofessional Phagocytosis Can Facilitate Herpesvirus Entry into Ocular Cells
title_fullStr Nonprofessional Phagocytosis Can Facilitate Herpesvirus Entry into Ocular Cells
title_full_unstemmed Nonprofessional Phagocytosis Can Facilitate Herpesvirus Entry into Ocular Cells
title_sort nonprofessional phagocytosis can facilitate herpesvirus entry into ocular cells
publisher Hindawi Limited
series Clinical and Developmental Immunology
issn 1740-2522
1740-2530
publishDate 2012-01-01
description Phagocytosis is a major mechanism by which the mediators of innate immunity thwart microbial infections. Here we demonstrate that human herpesviruses may have evolved a common mechanism to exploit a phagocytosis-like entrapment to gain entry into ocular cells. While herpes simplex virus-1 (HSV-1) causes corneal keratitis, cytomegalovirus (CMV) is associated with retinitis in immunocompromised individuals. A third herpesvirus, human herpesvirus-8 (HHV-8), is crucial for the pathogenesis of Kaposi’s sarcoma, a common AIDS-related tumor of eyelid and conjunctiva. Using laser scanning confocal microscopy, we show that successful infection of ocular cell types by all the three viruses, belonging to three divergent subfamilies of herpesviruses, is facilitated by induction of F-actin rich membrane protrusions. Inhibitors of F-actin polymerization and membrane protrusion formation, cytochalasin D and latrunculin B, were able to block infection by all three viruses. Similar inhibition was seen by blocking phosphoinositide 3 kinase signaling, which is required for microbial phagocytosis. Transmission electron microscopy data using human corneal fibroblasts for HSV-1, human retinal pigment epithelial cells for CMV, and human conjunctival epithelial cells for HHV-8 are consistent with the possibility that pseudopod-like membrane protrusions facilitate virus uptake by the ocular cells. Our findings suggest a novel mechanism by which the nonprofessional mediators of phagocytosis can be infected by human herpesviruses.
url http://dx.doi.org/10.1155/2012/651691
work_keys_str_mv AT vaibhavtiwari nonprofessionalphagocytosiscanfacilitateherpesvirusentryintoocularcells
AT deepakshukla nonprofessionalphagocytosiscanfacilitateherpesvirusentryintoocularcells
_version_ 1725484461349404672