Infection of human dendritic cells with recombinant vaccinia virus MVA reveals general persistence of viral early transcription but distinct maturation-dependent cytopathogenicity.
Vector-infected dendritic cells (DC) are evaluated for antigen delivery in experimental therapy of cancer and infectious diseases. Here, we investigated infections of immature or mature, monocyte-derived human DC with recombinant vaccinia virus MVA producing human Her-2/neu, a candidate tumor-associated antigen. Assessment of the molecular virus life cycle in infected DC revealed a general arrest at the level of viral early gene expression. When monitoring the phenotype of MVA-infected DC, including expression of cell surface markers, we found immature cells readily undergoing apoptosis. Nevertheless, we detected significant populations of viable DC being characterized by high level Her-2/neu expression and unimpaired display of costimulatory molecules. While infected viable immature DC failed to undergo maturation despite cytokine treatment, both DC populations efficiently presented MVA-produced target antigen. These findings allow to better define the requirements for MVA-mediated antigen delivery to DC and help to derive optimized vectors for this advanced therapy option.
Kastenmuller
Wolfgang
W
GSF-Institut für Molekulare Virologie, Klinikum rechts der Isar, Technische Universität 81675 München, Germany.
Drexler
Ingo
I
Ludwig
Holger
H
Erfle
Volker
V
Peschel
Christian
C
Bernhard
Helga
H
Sutter
Gerd
G
D017209:Apoptosis; D003713:Dendritic Cells / Q000166:cytology / Q000502:physiology / Q000821:virology*; D018734:Genes, erbB-2; D006801:Humans; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D011995:Recombination, Genetic; D014158:Transcription, Genetic; D014616:Vaccinia virus / Q000235:genetics* / Q000472:pathogenicity* / Q000502:physiology; D014779:Virus Replication
D018719:Erb-b2 Receptor Tyrosine Kinases