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Replication Vesicles are Load- and Choke-Points in the Hepatitis C Virus Lifecycle
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نویسنده
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binder m. ,sulaimanov n. ,clausznitzer d. ,schulze m. ,hüber c.m. ,lenz s.m. ,schlöder j.p. ,trippler m. ,bartenschlager r. ,lohmann v. ,kaderali l.
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منبع
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plos pathogens - 2013 - دوره : 9 - شماره : 8
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چکیده
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Hepatitis c virus (hcv) infection develops into chronicity in 80% of all patients,characterized by persistent low-level replication. to understand how the virus establishes its tightly controlled intracellular rna replication cycle,we developed the first detailed mathematical model of the initial dynamic phase of the intracellular hcv rna replication. we therefore quantitatively measured viral rna and protein translation upon synchronous delivery of viral genomes to host cells,and thoroughly validated the model using additional,independent experiments. model analysis was used to predict the efficacy of different classes of inhibitors and identified sensitive substeps of replication that could be targeted by current and future therapeutics. a protective replication compartment proved to be essential for sustained rna replication,balancing translation versus replication and thus effectively limiting rna amplification. the model predicts that host factors involved in the formation of this compartment determine cellular permissiveness to hcv replication. in gene expression profiling,we identified several key processes potentially determining cellular hcv replication efficiency. © 2013 binder et al.
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آدرس
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heidelberg university,medical faculty,department of infectious diseases,molecular virology,heidelberg, Germany, technische universität dresden,institute for medical informatics and biometry,dresden,germany,heidelberg university,viroquant research group modeling,bioquant bq26,heidelberg, Germany, technische universität dresden,institute for medical informatics and biometry,dresden, Germany, technische universität dresden,institute for medical informatics and biometry,dresden, Germany, heidelberg university,medical faculty,department of infectious diseases,molecular virology,heidelberg,germany,department of obstetrics and gynaecology,university of cambridge clinical school,the rosie hospital,cambridge, United Kingdom, heidelberg university,interdisciplinary center for scientific computing (iwr),simulation and optimization group,heidelberg, Germany, heidelberg university,interdisciplinary center for scientific computing (iwr),simulation and optimization group,heidelberg, Germany, university hospital of essen,department of gastroenterology and hepatology,essen, Germany, heidelberg university,medical faculty,department of infectious diseases,molecular virology,heidelberg, Germany, heidelberg university,medical faculty,department of infectious diseases,molecular virology,heidelberg, Germany, technische universität dresden,institute for medical informatics and biometry,dresden,germany,heidelberg university,viroquant research group modeling,bioquant bq26,heidelberg, Germany
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Authors
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