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

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• 作者：Wolfgang Kastenmuller ; Ingo Drexler ; Holger Ludwig ; Volker Erfle ; Christian Peschel ; Helga Bernhard and Gerd Sutter
• 关键词：Poxvirus ; Vector ; Gene expression ; Antigen presentation ; Tumor antigen ; Immunotherapy
• 刊名：Virology
• 出版年：2006
• 出版时间：5 July 2006
• 年：2006
• 卷：350
• 期：2
• 页码：276-288
• 全文大小：1305 K

文摘

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.