title: Murine Bone Marrow-Derived Dendritic Cells Transduced by Light-Helper-Dependent Herpes Simplex Virus-1 Amplicon Vector Acquire a Mature Dendritic Cell Phenotype.
abstract: Dendritic cells (DCs) turn into the most potent antigen-presenting cells following a complex transforming process, which leads to their maturation. Herpes simplex virus-1 (HSV-1) amplicon vectors represent highly versatile viral vector platforms with the ability to transduce immature DCs at exceedingly high efficiencies, while the efficiency of infection of mature DCs is significantly low. However, the bacterial artificial chromosome (BAC)-dependent (BD) amplicon vectors tested so far do not result in the maturation of mouse bone marrow-derived DCs (BMDCs) in vitro. In this study we investigated the effects of light-helper-dependent (LHD) amplicon vectors produced with the replication-defective HSV-1 LaLΔJ helper virus system. First, we observed that transgene expression in BMDC cultures was equally potent between the LHD and the BD amplicon vectors. We determined that the percentage of transduced cells and the duration of transgene expression were negatively influenced by the presence of increasing levels of helper virus. Second, infection by the LHD amplicon vector as well as the helper HSV-1 LaLΔJ virus alone resulted in the phenotypic maturation of BMDCs and the expression of both interferon-stimulated genes and proinflammatory cytokines. Further comparisons of the gene expression of infected DCs showed that while interferon-stimulated genes such as Ifit1, Ifit3, Mx2, Isg15, and Cxcl10 were induced by both BD and LHD amplicon vectors, early proinflammatory cytokine gene expression (Tnfa, Il1a, Il1b, Il6, Il10, Il12b, Cxcl1, and Cxcl16) and DC maturation were mediated only by the LHD amplicons.
authors.affiliation: 1 Molecular Virology Laboratory, Hellenic Pasteur Institute , 11521 Athens, Greece .|2 Department of Biophysics, School of Medicine, Acibadem University , 34848 Istanbul, Turkey .
authors.forename: Devrim
authors.initials: D
authors.lastname: Oz-Arslan
authors.affiliation: 1 Molecular Virology Laboratory, Hellenic Pasteur Institute , 11521 Athens, Greece .|3 Laboratory of Cellular and Molecular Pneumonology, Medical School, University of Crete , 70013 Crete, Greece .
authors.forename: Eliza
authors.initials: E
authors.lastname: Tsitoura
authors.affiliation: 1 Molecular Virology Laboratory, Hellenic Pasteur Institute , 11521 Athens, Greece .
authors.forename: Dorothea
authors.initials: D
authors.lastname: Kazazi
authors.affiliation: 1 Molecular Virology Laboratory, Hellenic Pasteur Institute , 11521 Athens, Greece .
authors.forename: Vlasis
authors.initials: V
authors.lastname: Kouvatsis
authors.affiliation: 4 UMR 1179 INSERM-UVSQ-End-icap, Handicap Neuromusculaire, Biotherapie et Pharmacologie appliquées, UFR des sciences de la santé "Simone Veil," Université de Versailles-Saint Quentin en Yvelines , 78180 Montigny-le-Bretonneux, France .
authors.forename: Alberto L
authors.initials: AL
authors.lastname: Epstein
authors.affiliation: 1 Molecular Virology Laboratory, Hellenic Pasteur Institute , 11521 Athens, Greece .|5 Department of Molecular Biology and Genetics, Democritus University of Thrace , 68100 Alexandroupolis, Greece .
authors.forename: Penelope
authors.initials: P
authors.lastname: Mavromara
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002522:Chlorocebus aethiops; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D003713:Dendritic Cells / Q000166:cytology* / Q000378:metabolism; D005822:Genetic Vectors / Q000235:genetics; D006378:Helper Viruses / Q000235:genetics*; D018259:Herpesvirus 1, Human / Q000235:genetics*; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010641:Phenotype; D014161:Transduction, Genetic; D014709:Vero Cells
chemical_list: D016207:Cytokines