engleski

Cytomegalovirus Infection in Mice Caused by Bacteria Carring a Cloned MCMV Genome

Bacterial delivery systems are gaining increasing interest as potential vaccination vectors to deliver either proteins or nucleic acids for gene expression in the recipient. Bacterial delivery systems for gene expression usually contain small multicopy plasmids. We addressed the question of whether bacteria containing a single plasmid with a complete cytomegaloviral genome could reconstitute the viral replication process in vivo, and whether this would lead to specific immunity against the virus. We have cloned the murine cytomegalovirus (MCMV) genome as a bacterial artificial chromosome (BAC) maintained in E. coli. Here we show that the MCMV-BAC can be stably maintained in various strains of Salmonella typhimurium as well. Further, we show that both the S. typhimurium and E. coli, harboring the single copy MCMV-BAC reconstituted virus infection upon injection into interferon-gamma receptor deficient mice. This led to elevated titers of specific anti-MCMV antibodies, protetion against lethal MCMV challenge and strong expression of additional genes introduced into the viral genome. Thus, the reconstitution of infectious virus from live attentuated bacteria presents a novel concept for studying the potential of multivalent virus vaccines launched from bacterial vectors.

cytomegalovirus; infection

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