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          Institute: MPI für biophysikalische Chemie     Collection: Abteilungsunabhängige Arbeitsgruppen     Display Documents

ID: 17051.0, MPI für biophysikalische Chemie / Abteilungsunabhängige Arbeitsgruppen
Evolution of bacteriophage in continuous culture: a model system to test antiviral gene therapies for the emergence of phage escape mutants
Authors:Lindemann, B. F.; Klug, C.; Schwienhorst, A.
Date of Publication (YYYY-MM-DD):2002-06
Title of Journal:Journal of Virology
Issue / Number:11
Start Page:5784
End Page:5792
Review Status:Peer-review
Audience:Not Specified
Abstract / Description:The emergence of viral escape mutants is usually a highly undesirable phenomenon. This phenomenon is frequently observed in antiviral drug applications for the treatment of viral infections and can undermine long-term therapeutic success. Here, we propose a strategy for evaluating a given antiviral approach in terms of its potential to provoke the appearance of resistant virus mutants. By use of Q(3 RNA phage as a model system, the effect of an antiviral gene therapy, i.e., a virus- specific repressor protein expressed by a recombinant Escherichia coli host, was studied over the course of more than 100 generations. In 13 experiments carried out in parallel, 12 phage populations became resistant and 1 became extinct. Sequence analysis revealed that only two distinct phage mutants emerged in the 12 surviving phage populations. For both escape mutants, sequence variations located in the repressor binding site of the viral genomic RNA, which decrease affinity for the repressor protein, conferred resistance to translational repression. The results clearly suggest the feasibility of the proposed strategy for the evaluation of antiviral approaches in terms of their potential to allow resistant mutants to appear. In addition, the strategy proved to be a valuable tool for observing virus-specific molecular targets under the impact of antiviral drugs.
Comment of the Author/Creator:Date: 2002, JUN
External Publication Status:published
Document Type:Article
Communicated by:N. N.
Affiliations:MPI für biophysikalische Chemie/EG Manfred Eigen
External Affiliations:Univ Gottingen, Inst Genet & Mikrobiol, Abt Mol Genet &; Praeparat Mol Biol, Grisebachstr 8, D-37077 Gottingen, Germany
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