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Basic Characteristics of Mutations
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Mutation Site
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G28A |
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Mutation Site Sentence
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Naturally occurring HCV isolates encoding G28A are similarly resistant to miR-122 inhibition, indicating that subtle differences in viral sequence, even outside the seed-binding site, greatly influence HCV's miR-122 concentration requirement. |
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Mutation Level
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Nucleotide level |
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Mutation Type
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Gene/Protein/Region
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5'UTR |
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Standardized Encoding Gene
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Genotype/Subtype
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- |
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Viral Reference
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-
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Functional Impact and Mechanisms
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Disease
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Cell line
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Immune
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- |
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Target Gene
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MIR122
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Clinical and Epidemiological Correlations
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Clinical Information
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- |
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Treatment
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- |
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Location
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- |
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Literature Information
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PMID
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25403145
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Title
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Hepatitis C virus genetics affects miR-122 requirements and response to miR-122 inhibitors
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Author
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Israelow B,Mullokandov G,Agudo J,Sourisseau M,Bashir A,Maldonado AY,Dar AC,Brown BD,Evans MJ
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Journal
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Nature communications
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Journal Info
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2014 Nov 18;5:5408
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Abstract
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Hepatitis C virus (HCV) replication is dependent on a liver-specific microRNA (miRNA), miR-122. A recent clinical trial reported that transient inhibition of miR-122 reduced viral titres in HCV-infected patients. Here we set out to better understand how miR-122 inhibition influences HCV replication over time. Unexpectedly, we observed the emergence of an HCV variant that is resistant to miR-122 knockdown. Next-generation sequencing revealed that this was due to a single nucleotide change at position 28 (G28A) of the HCV genome, which falls between the two miR-122 seed-binding sites. Naturally occurring HCV isolates encoding G28A are similarly resistant to miR-122 inhibition, indicating that subtle differences in viral sequence, even outside the seed-binding site, greatly influence HCV's miR-122 concentration requirement. In addition, we found that HCV itself reduces miR-122's activity in the cell, possibly through binding and sequestering miR-122. Our study provides insight into the interaction between miR-122 and HCV, including viral adaptation to reduced miR-122 bioavailability, and has implications for the development of anti-miR-122-based HCV drugs.
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Sequence Data
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-
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