Virusinduzierte Fusion zur Beseitigung von Tumorzellen

Adenovirus-Vektoren können zur Expression von Fusionsproteine eingesetzt werden, um neue Strategien zur Beseitigung maligner Tumoren zu entwickeln. Dazu ist zunächst zu klären, wie eine Fusion infizierter Zellen die Replikation und Zytotoxizität onkolytischer Adenoviren beeinflusst. Um diese Fragen...

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Autor Principal: Horn, Germán Pedro
Outros autores: Dobbelstein, Matthias (PD Dr.med) (BetreuerIn (Doktorarbeit))
Formato: Dissertation
Idioma:German
Publicado: Philipps-Universität Marburg 2005
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The efficiency of viruses in cancer therapy is enhanced by proteins that mediate the fusion of infected cells with their neighbors. It was reported that replication-competent adenovirus particles can spread between nuclei within fusion-generated syncytia. To assess this conjecture, we generated fusogenic adenoviruses that express a balanced ratio of the F and H glycoproteins of measles virus. The viruses displayed enhancedcytotoxicity but largely unchanged replication efficiencies compared to a nonfusogenic virus. Most notably, thevirus genomes did not spread through fusion-generated multinuclear cells. Hence, adenovirus replication insyncytia remains largely restricted to initially transduced nuclei.