scholarly journals Infection of mature dendritic cells with herpes simplex virus type 1 dramatically reduces lymphoid chemokine-mediated migration

2005 ◽  
Vol 86 (6) ◽  
pp. 1645-1657 ◽  
Author(s):  
Alexander T. Prechtel ◽  
Nadine M. Turza ◽  
Dieter J. Kobelt ◽  
Jutta I. Eisemann ◽  
Robert S. Coffin ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Antiviral Immune Response ◽  
Migration Assays ◽  
Simplex Virus ◽  
Hsv 1

Herpes simplex virus type 1 (HSV-1) is able to establish latency in infected individuals. In order to characterize potential new immune-escape mechanisms, mature dendritic cells (DCs) were infected with HSV-1 and total cellular RNA was isolated from infected and mock-infected populations at different time points. RNA profiling on Affymetrix Human Genome U133A arrays demonstrated a dramatic downregulation of the migration-mediating surface molecules CCR7 and CXCR4, an observation that was further confirmed by RT-PCR and fluorescence-activated cell sorting analyses. Furthermore, migration assays revealed that, upon infection of mature DCs, CCR7- and CXCR4-mediated migration towards the corresponding CCL19 and CXCL12 chemokine gradients was strongly reduced. It is noteworthy that the infection of immature DCs with HSV-1 prior to maturation led to a failure of CCR7 and CXCR4 upregulation during DC maturation and, as a consequence, also induced a block in their migratory capacity. Additional migration assays with a Δvhs mutant virus lacking the virion host shutoff (vhs) gene, which is known to degrade cellular mRNAs, suggested a vhs-independent mechanism. These results indicate that HSV-1-infected mature DCs are limited in their capacity to migrate to secondary lymphoid organs, the areas of antigen presentation and T-cell stimulation, thus inhibiting an antiviral immune response. This represents a novel, previously unrecognized mechanism for HSV-1 to escape the human immune system.

scholarly journals Infection of dendritic cells with herpes simplex virus type 1 induces rapid degradation of CYTIP, thereby modulating adhesion and migration

Blood ◽  
2011 ◽  
Vol 118 (1) ◽  
pp. 107-115 ◽  
Author(s):  
Alexandros A. Theodoridis ◽  
Christina Eich ◽  
Carl G. Figdor ◽  
Alexander Steinkasserer
Keyword(s):  
Dendritic Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Immune Responses ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Lymphoid Tissues ◽  
Simplex Virus ◽  
Hsv 1

Abstract Immune responses require spatial and temporal coordinated interactions between different cell types within distinct microenvironments. This dynamic interplay depends on the competency of the involved cells, predominantly leukocytes, to actively migrate to defined sites of cellular encounters in various tissues. Because of their unique capacity to transport antigen from the periphery to secondary lymphoid tissues for the activation of naive T cells, dendritic cells (DCs) play a key role in the initiation and orchestration of adaptive immune responses. Therefore, pathogen-mediated interference with this process is a very effective way of immune evasion. CYTIP (cytohesin-interacting protein) is a key regulator of DC motility. It has previously been described to control LFA-1 deactivation and to regulate DC adherence. CYTIP expression is up-regulated during DC maturation, enabling their transition from the sessile to the motile state. Here, we demonstrate that on infection of human monocyte-derived DCs with herpes simplex virus type 1 (HSV-1), CYTIP is rapidly degraded and as a consequence β-2 integrins, predominantly LFA-1, are activated. Furthermore, we show that the impairment of migration in HSV-1-infected DCs is in part the result of this increased integrin-mediated adhesion. Thus, we propose a new mechanism of pathogen-interference with central aspects of leukocyte biology.

scholarly journals Pharmacological Inhibition of IRE-1 Alpha Activity in Herpes Simplex Virus Type 1 and Type 2-Infected Dendritic Cells Enhances T Cell Activation

2022 ◽  
Vol 12 ◽  
Author(s):  
Eduardo I. Tognarelli ◽  
Angello Retamal-Díaz ◽  
Mónica A. Farías ◽  
Luisa F. Duarte ◽  
Tomás F. Palomino ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
T Cell ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Simplex Virus ◽  
Hsv 1

Herpes simplex virus type 1 (HSV-1) and type 2 (HSV-2) infections are life-long and highly prevalent in the human population. These viruses persist in the host, eliciting either symptomatic or asymptomatic infections that may occur sporadically or in a recurrent manner through viral reactivations. Clinical manifestations due to symptomatic infection may be mild such as orofacial lesions, but may also translate into more severe diseases, such as ocular infections that may lead to blindness and life-threatening encephalitis. A key feature of herpes simplex viruses (HSVs) is that they have evolved molecular determinants that hamper numerous components of the host’s antiviral innate and adaptive immune system. Importantly, HSVs infect and negatively modulate the function of dendritic cells (DCs), by inhibiting their T cell-activating capacity and eliciting their apoptosis after infection. Previously, we reported that HSV-2 activates the splicing of the mRNA of XBP1, which is related to the activity of the unfolded protein response (UPR) factor Inositol-Requiring Enzyme 1 alpha (IRE-1α). Here, we sought to evaluate if the activation of the IRE-1α pathway in DCs upon HSV infection may be related to impaired DC function after infection with HSV-1 or HSV-2. Interestingly, the pharmacological inhibition of the endonuclease activity of IRE-1α in HSV-1- and HSV-2-infected DCs significantly reduced apoptosis in these cells and enhanced their capacity to migrate to lymph nodes and activate virus-specific CD4+ and CD8+ T cells. These findings suggest that the activation of the IRE-1α-dependent UPR pathway in HSV-infected DCs may play a significant role in the negative effects that these viruses exert over these cells and that the modulation of this signaling pathway may be relevant for enhancing the function of DCs upon infection with HSVs.

scholarly journals Infectivity of herpes simplex virus type-1 (HSV-1) amplicon vectors in dendritic cells is determined by the helper virus strain used for packaging

2007 ◽  
Vol 145 (1) ◽  
pp. 37-46 ◽  
Author(s):  
Kathlyn Santos ◽  
Christine M. Sanfilippo ◽  
Wade C. Narrow ◽  
Ann E. Casey ◽  
Sol M. Rodriguez-Colon ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Virus Strain ◽  
Herpes Simplex Virus Type ◽  
Helper Virus ◽  
Simplex Virus ◽  
Hsv 1

scholarly journals Role of Dendritic Cells in Enhancement of Herpes Simplex Virus Type 1 Latency and Reactivation in Vaccinated Mice

2008 ◽  
Vol 15 (12) ◽  
pp. 1859-1867 ◽  
Author(s):  
Kevin R. Mott ◽  
Homayon Ghiasi
Keyword(s):  
Dendritic Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Diphtheria Toxin ◽  
Corneal Scarring ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Ocular infection with herpes simplex virus type 1 (HSV-1) frequently leads to recurrent infection, which is a major cause of corneal scarring. Thus, the prevention of the establishment of latency should be a primary goal of vaccination against HSV-1. To this end, we have examined the contribution of dendritic cells (DCs) to the efficacy of a vaccine against ocular HSV-1 infection. Transgenic mice (expressing a CD11c-diphtheria toxin receptor-green fluorescent protein construct) with a BALB/c background were immunized with a vaccine consisting of DNA that encodes five HSV-1 glycoproteins or were immunized with vector control DNA. The vaccinated mice were then depleted of their DCs through the injection of diphtheria toxin before and after ocular challenge with HSV-1. Analyses of HSV-1 replication in the eye, blepharitis, corneal scarring, and the survival of the infected mice upon primary infection indicated that DC depletion neither promoted nor compromised the efficacy of the vaccine. In contrast, DC depletion was associated with an approximately fivefold reduction in the level of latent virus in the trigeminal ganglia (TGs) of latently infected mice, as well as a significant reduction in the reactivation rate of latent virus. The possibility that DCs enhance the latency of HSV-1 in the TGs of ocularly infected mice suggests for the first time that DCs, rather than acting as “immune saviors,” can exacerbate disease and compromise vaccine efficacy by enhancing viral latency and reactivation.

scholarly journals Lymphoid-Related CD11c+ CD8α+ Dendritic Cells Are Involved in Enhancing Herpes Simplex Virus Type 1 Latency

2008 ◽  
Vol 82 (20) ◽  
pp. 9870-9879 ◽  
Author(s):  
Kevin R. Mott ◽  
David UnderHill ◽  
Steven L. Wechsler ◽  
Homayon Ghiasi
Keyword(s):  
Dendritic Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Ex Vivo ◽  
Macrophage Colony ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT The mechanism(s) by which herpes simplex virus type 1 (HSV-1) latency is established in neurons is not known. In this study, we examined the effect of dendritic cells (DCs) on the level of HSV-1 latency in trigeminal ganglia (TGs) of ocularly infected BALB/c and C57BL/6 mice. We found that immunization of wild-type mice with FMS-like tyrosine kinase 3 ligand (Flt3L) DNA, which increases the number of DCs, increased the amount of latency in infected mice. Conversely, depletion of DCs was associated with reduced latency. Latency was also significantly reduced in Flt3L−/− and CD8−/− mice. Interestingly, immunization of Flt3L−/− but not CD8−/− mice with Flt3L DNA increased latency. Transfer experiments using DCs expanded ex vivo with Flt3L or granulocyte-macrophage colony-stimulating factor suggested that increased latency was associated with the presence of lymphoid-related (CD11c+ CD8α+) DCs, while reduced latency was associated with myeloid-related (CD11c+ CD8α−) DCs. Modulation of DC numbers by Flt3L DNA immunization or depletion did not alter acute virus replication in the eye or TG or eye disease in ocularly infected mice. Our results suggest that CD11c+ CD8α+ DCs directly or indirectly increase the amount of HSV-1 latency in mouse TGs.

scholarly journals Herpes Simplex Virus Type 1 Induces CD83 Degradation in Mature Dendritic Cells with Immediate-Early Kinetics via the Cellular Proteasome

2007 ◽  
Vol 81 (12) ◽  
pp. 6326-6338 ◽  
Author(s):  
Mirko Kummer ◽  
Nadine M. Turza ◽  
Petra Muhl-Zurbes ◽  
Matthias Lechmann ◽  
Chris Boutell ◽  
...  
Keyword(s):  
Dendritic Cells ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Cell Surface ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Surface Expression ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Mature dendritic cells (DCs) are the most potent antigen-presenting cells within the human immune system. However, Herpes simplex virus type 1 (HSV-1) is able to interfere with DC biology and to establish latency in infected individuals. In this study, we provide new insights into the mechanism by which HSV-1 disarms DCs by the manipulation of CD83, a functionally important molecule for DC activation. Fluorescence-activated cell sorter (FACS) analyses revealed a rapid downmodulation of CD83 surface expression within 6 to 8 h after HSV-1 infection, in a manner strictly dependent on viral gene expression. Soluble CD83 enzyme-linked immunosorbent assays, together with Western blot analysis, demonstrated that CD83 rapidly disappears from the cell surface after contact with HSV-1 by a mechanism that involves protein degradation rather than shedding of CD83 from the cell surface into the medium. Infection experiments with an ICP0 deletion mutant demonstrated an important role for this viral immediate-early protein during CD83 degradation, since this particular mutant strain leads to strongly reduced CD83 degradation. This hypothesis was further strengthened by cotransfection of plasmids expressing CD83 and ICP0 into 293T cells, which led to significantly reduced accumulation of CD83. In strong contrast, transfection of plasmids expressing CD83 and a mutant ICP0 defective in its RING finger-mediated E3 ubiquitin ligase function did not reduce CD83 expression. Inhibition of the proteasome, the cellular protein degradation machinery, almost completely restored CD83 surface expression during HSV-1 infection, indicating that proteasome-mediated degradation and HSV-1 ICP0 play crucial roles in this novel viral immune escape mechanism.

Herpes simplex virus type 1 (HSV-1) infects mature dendritic cells (DCs) in colonic explants from Crohn's disease

2003 ◽  
Vol 124 (4) ◽  
pp. A499 ◽  
Author(s):  
Manuel Silva ◽  
Carolina Lopez ◽  
Jose Menezes ◽  
Paulo Cordeiro ◽  
Ernest Seidman
Keyword(s):  
Dendritic Cells ◽  
Crohn’S Disease ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Crohn's Disease ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Simplex Virus ◽  
Hsv 1

scholarly journals Herpes Simplex Virus Type 1–Encoded miR-H2-3p Manipulates Cytosolic DNA–Stimulated Antiviral Innate Immune Response by Targeting DDX41

Viruses ◽  
2019 ◽  
Vol 11 (8) ◽  
pp. 756 ◽  
Author(s):  
Yongzhong Duan ◽  
Jieyuan Zeng ◽  
Shengtao Fan ◽  
Yun Liao ◽  
Min Feng ◽  
...  
Keyword(s):  
Immune Response ◽  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Dna Sensor ◽  
Antiviral Immune Response ◽  
Simplex Virus ◽  
Hsv 1

Herpes simplex virus type 1 (HSV-1), one of the human pathogens widely epidemic and transmitted among various groups of people in the world, often causes symptoms known as oral herpes or lifelong asymptomatic infection. HSV-1 employs many sophisticated strategies to escape host antiviral immune response based on its multiple coding proteins. However, the functions involved in the immune evasion of miRNAs encoded by HSV-1 during lytic (productive) infection remain poorly studied. Dual-luciferase reporter gene assay and bioinformatics revealed that Asp-Glu-Ala-Asp (DEAD)-box helicase 41 (DDX41), a cytosolic DNA sensor of the DNA-sensing pathway, was a putative direct target gene of HSV-1-encoded miR-H2-3p. The transfection of miR-H2-3p mimics inhibited the expression of DDX41 at the level of mRNA and protein, as well as the expression of interferon beta (IFN-β) and myxoma resistance protein I (MxI) induced by HSV-1 infection in THP-1 cells, and promoted the viral replication and its gene transcription. However, the transfection of miR-H2-3p inhibitor showed opposite effects. This finding indicated that HSV-1-encoded miR-H2-3p attenuated cytosolic DNA–stimulated antiviral immune response by manipulating host DNA sensor molecular DDX41 to enhance virus replication in cultured cells.

scholarly journals Herpes Simplex Virus Type 1 Evades the Effects of Antibody and Complement In Vivo

2002 ◽  
Vol 76 (18) ◽  
pp. 9232-9241 ◽  
Author(s):  
John M. Lubinski ◽  
Ming Jiang ◽  
Lauren Hook ◽  
Yueh Chang ◽  
Chad Sarver ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Virus Type ◽  
Immune Evasion ◽  
Herpes Simplex Virus Type ◽  
Complement Components ◽  
Simplex Virus ◽  
Hsv 1

ABSTRACT Herpes simplex virus type 1 (HSV-1) encodes a complement-interacting glycoprotein, gC, and an immunoglobulin G (IgG) Fc binding glycoprotein, gE, that mediate immune evasion by affecting multiple aspects of innate and acquired immunity, including interfering with complement components C1q, C3, C5, and properdin and blocking antibody-dependent cellular cytotoxicity. Previous studies evaluated the individual contributions of gC and gE to immune evasion. Experiments in a murine model that examines the combined effects of gC and gE immune evasion on pathogenesis are now reported. Virulence of wild-type HSV-1 is compared with mutant viruses defective in gC-mediated C3 binding, gE-mediated IgG Fc binding, or both immune evasion activities. Eliminating both activities greatly increased susceptibility of HSV-1 to antibody and complement neutralization in vitro and markedly reduced virulence in vivo as measured by disease scores, virus titers, and mortality. Studies with C3 knockout mice indicated that other activities attributed to these glycoproteins, such as gC-mediated virus attachment to heparan sulfate or gE-mediated cell-to-cell spread, do not account for the reduced virulence of mutant viruses. The results support the importance of gC and gE immune evasion in vivo and suggest potential new targets for prevention and treatment of HSV disease.

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