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Journal articles
Synonymous mutations in the core gene are linked to unusual serological profile in hepatitis C virus infection.
Abstract : 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 antit-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.
Cited literature [42 references]
https://hal-riip.archives-ouvertes.fr/pasteur-00562342
Contributor : Agata Budkowska Connect in order to contact the contributor
Submitted on : Thursday, February 3, 2011 - 10:44:23 AM
Last modification on : Monday, November 22, 2021 - 5:46:02 PM
Long-term archiving on: : Saturday, December 3, 2016 - 7:10:23 PM
Contributor : Agata Budkowska Connect in order to contact the contributor
Submitted on : Thursday, February 3, 2011 - 10:44:23 AM
Last modification on : Monday, November 22, 2021 - 5:46:02 PM
Long-term archiving on: : Saturday, December 3, 2016 - 7:10:23 PM
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journal.pone.0015871.pdf
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