Document Detail

The virological synapse facilitates herpes simplex virus entry into T cells.
MedLine Citation:
PMID:  19339346     Owner:  NLM     Status:  MEDLINE    
The virological synapse (VS) is a specialized molecular structure that facilitates the transfer of certain lymphotropic viruses into uninfected T cells. However, the role of the VS in the transfer of nonlymphotropic viruses into T cells is unknown. Herpes simplex virus (HSV) has been shown in vitro to infect T cells and modulate T-cell receptor function, thereby suppressing T-cell antiviral function. However, whether such infection of T cells occurs in vivo is unknown. Here, we examined whether T-cell infection could be observed in human HSV disease and investigated the mechanism of HSV entry into T cells. We found that HSV-infected T cells were readily detectable during human disease, suggesting that infection and modulation of T-cell function plays a role in human immunopathology. HSV infection of both CD4(+) and CD8(+) T cells occurred much more efficiently via direct cell-to-cell spread from infected fibroblasts than by cell-free virus. Activation of T cells increased their permissivity to HSV infection. Cell-to-cell spread to T cells did not require HSV glycoproteins E and I (gE and gI), which are critical for cell-to-cell spread between epithelial cells. Transfer of HSV to T cells required gD, and the four known entry receptors appear to be contributing to viral entry, with a dominant role for the herpesvirus entry mediator and nectin-1. VS-like structures enriched in activated lymphocyte function-associated antigen 1 (LFA-1) were observed at the point of contact between HSV-infected fibroblasts and T cells. Consistent with spread occurring via the VS, transfer of HSV was increased by activation of LFA-1, and cell-to-cell spread could be inhibited by antibodies to LFA-1 or gD. Taken together, these results constitute the first demonstration of VS-dependent cell-to-cell spread for a predominantly nonlymphotropic virus. Furthermore, they support an important role for infection and immunomodulation of T cells in clinical human disease. Targeting of the VS might allow selective immunopotentiation during infections with HSV or other nonlymphotropic viruses.
Martine Aubert; Miri Yoon; Derek D Sloan; Patricia G Spear; Keith R Jerome
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2009-04-01
Journal Detail:
Title:  Journal of virology     Volume:  83     ISSN:  1098-5514     ISO Abbreviation:  J. Virol.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-05-21     Completed Date:  2009-05-28     Revised Date:  2010-09-23    
Medline Journal Info:
Nlm Unique ID:  0113724     Medline TA:  J Virol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6171-83     Citation Subset:  IM    
Vaccine and Infectious Disease Institute, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA.
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MeSH Terms
Cell Adhesion Molecules / metabolism
Cercopithecus aethiops
Fibroblasts / virology
Herpes Simplex / immunology,  virology*
Herpesvirus 1, Human / immunology,  physiology*
Jurkat Cells
Lymphocyte Activation
Receptors, Tumor Necrosis Factor, Member 14 / metabolism
T-Lymphocytes / virology*
Vero Cells
Viral Envelope Proteins / metabolism
Virus Internalization*
Grant Support
Reg. No./Substance:
0/Cell Adhesion Molecules; 0/Receptors, Tumor Necrosis Factor, Member 14; 0/Viral Envelope Proteins; 0/glycoprotein gD, herpes simplex virus type 1; 0/nectins

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