title: Infection of mature dendritic cells with herpes simplex virus type 1 dramatically reduces lymphoid chemokine-mediated migration.
abstract: 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 Deltavhs 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.
authors.affiliation: Department of Dermatology, University Hospital Erlangen, Hartmannstrasse 14, D-91052 Erlangen, Germany.
authors.forename: Alexander T
authors.initials: AT
authors.lastname: Prechtel
authors.affiliation: Department of Dermatology, University Hospital Erlangen, Hartmannstrasse 14, D-91052 Erlangen, Germany.
authors.forename: Nadine M
authors.initials: NM
authors.lastname: Turza
authors.affiliation: Department of Dermatology, University Hospital Erlangen, Hartmannstrasse 14, D-91052 Erlangen, Germany.
authors.forename: Dieter J
authors.initials: DJ
authors.lastname: Kobelt
authors.affiliation: Department of Dermatology, University Hospital Erlangen, Hartmannstrasse 14, D-91052 Erlangen, Germany.
authors.forename: Jutta I
authors.initials: JI
authors.lastname: Eisemann
authors.affiliation: BioVex Ltd, Oxford OX14 4RX, UK.|Department of Immunology and Molecular Pathology, University College London, London W1P 6DB, UK.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Coffin
authors.affiliation: BioVex Ltd, Oxford OX14 4RX, UK.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: McGrath
authors.affiliation: Max Delbruck Center for Molecular Medicine, MDC, Robert-Rossle-Str. 10, 13092 Berlin, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Hacker
authors.affiliation: Institute for Biomedical Technology, Department of Cell Biology, University Hospital Aachen, Aachen, Germany.|Max Delbruck Center for Molecular Medicine, MDC, Robert-Rossle-Str. 10, 13092 Berlin, Germany.
authors.forename: Xinsheng
authors.initials: X
authors.lastname: Ju
authors.affiliation: Institute for Biomedical Technology, Department of Cell Biology, University Hospital Aachen, Aachen, Germany.|Max Delbruck Center for Molecular Medicine, MDC, Robert-Rossle-Str. 10, 13092 Berlin, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Zenke
authors.affiliation: Department of Dermatology, University Hospital Erlangen, Hartmannstrasse 14, D-91052 Erlangen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Steinkasserer
mesh_terms: D002454:Cell Differentiation; D002465:Cell Movement; D003713:Dendritic Cells / Q000166:cytology / Q000276:immunology*; D015536:Down-Regulation; D006561:Herpes Simplex / Q000276:immunology; D018259:Herpesvirus 1, Human / Q000276:immunology*; D006801:Humans; D009154:Mutation; D012333:RNA, Messenger / Q000032:analysis; D054400:Receptors, CCR7; D019718:Receptors, CXCR4 / Q000032:analysis / Q000235:genetics; D019707:Receptors, Chemokine / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012260:Ribonucleases; D013997:Time Factors; D014764:Viral Proteins / Q000235:genetics
chemical_list: C515370:CCR7 protein, human; D012333:RNA, Messenger; D054400:Receptors, CCR7; D019718:Receptors, CXCR4; D019707:Receptors, Chemokine; D014764:Viral Proteins; C070722:virion host shutoff protein, Simplexvirus; D012260:Ribonucleases