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Basic Characteristics of Mutations
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Mutation Site
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G363A |
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Mutation Site Sentence
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Additional mutations in SL337 might involve a G>A change at nucleotide 363, and T>C at 372, reducing the size of the upper terminal loop. |
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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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Standardized Encoding Gene
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Genotype/Subtype
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1a |
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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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HCV Infection
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Immune
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- |
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Target Gene
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-
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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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Cambodia |
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Literature Information
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PMID
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21283512
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Title
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Synonymous mutations in the core gene are linked to unusual serological profile in hepatitis C virus infection
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Author
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Budkowska A,Kakkanas A,Nerrienet E,Kalinina O,Maillard P,Horm SV,Dalagiorgou G,Vassilaki N,Georgopoulou U,Martinot M,Sall AA,Mavromara P
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Journal
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PloS one
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Journal Info
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2011 Jan 6;6(1):e15871
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Abstract
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The biological role of the protein encoded by the alternative open reading frame (core+1/ARF) of the Hepatitis C virus (HCV) genome remains elusive, as does the significance of the production of corresponding antibodies in HCV infection. We investigated the prevalence of anti-core and anti-core+1/ARFP antibodies in HCV-positive blood donors from Cambodia, using peptide and recombinant protein-based ELISAs. We detected unusual serological profiles in 3 out of 58 HCV positive plasma of genotype 1a. These patients were negative for anti-core antibodies by commercial and peptide-based assays using C-terminal fragments of core but reacted by Western Blot with full-length core protein. All three patients had high levels of anti-core+1/ARFP antibodies. Cloning of the cDNA that corresponds to the core-coding region from these sera resulted in the expression of both core and core+1/ARFP in mammalian cells. The core protein exhibited high amino-acid homology with a consensus HCV1a sequence. However, 10 identical synonymous mutations were found, and 7 were located in the aa(99-124) region of core. All mutations concerned the third base of a codon, and 5/10 represented a T>C mutation. Prediction analyses of the RNA secondary structure revealed conformational changes within the stem-loop region that contains the core+1/ARFP internal AUG initiator at position 85/87. Using the luciferase tagging approach, we showed that core+1/ARFP expression is more efficient from such a sequence than from the prototype HCV1a RNA. We provide additional evidence of the existence of core+1/ARFP in vivo and new data concerning expression of HCV core protein. We show that HCV patients who do not produce normal anti-core antibodies have unusually high levels of anti-core+1/ARFP and harbour several identical synonymous mutations in the core and core+1/ARFP coding region that result in major changes in predicted RNA structure. Such HCV variants may favour core+1/ARFP production during HCV infection.
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Sequence Data
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-
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