Infection of human dendritic cells with recombinant vaccinia virus MVA reveals general persistence of viral early transcription but distinct maturation-dependent cytopathogenicity

Virology. 2006 Jul 5;350(2):276-88. doi: 10.1016/j.virol.2006.02.039. Epub 2006 Apr 3.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis
  • Dendritic Cells / cytology
  • Dendritic Cells / physiology
  • Dendritic Cells / virology*
  • Genes, erbB-2
  • Humans
  • Receptor, ErbB-2 / genetics
  • Recombination, Genetic
  • Transcription, Genetic*
  • Vaccinia virus / genetics*
  • Vaccinia virus / pathogenicity*
  • Vaccinia virus / physiology
  • Virus Replication

Substances

  • Receptor, ErbB-2