Synonymous mutations in the core gene are linked to unusual serological profile in hepatitis C virus infection
| Autor: | Amadou A. Sall, Agata Budkowska, Urania Georgopoulou, Niki Vassilaki, Eric Nerrienet, Athanassios Kakkanas, Geena Dalagiorgou, Olga V. Kalinina, M. Martinot, Patrick Maillard, Srey Viseth Horm, Penelope Mavromara |
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| Přispěvatelé: | Hépacivirus et immunité innée, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institut Pasteur Hellénique, Réseau International des Instituts Pasteur (RIIP), Institut Pasteur du Cambodge, Institut Pasteur de Saint-Pétersbourg, Centre de recherche biomédicale Bichat-Beaujon (CRB3), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur de Dakar, Budkowska, Agata, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS) |
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
RNA viruses
Hepacivirus medicine.disease_cause Biochemistry Hepatitis Computational biology 0302 clinical medicine Molecular cell biology Viral classification Coding region RNA structure Immune Response 0303 health sciences Multidisciplinary biology Viral Core Proteins Microbial Mutation Hepatitis C 3. Good health Nucleic acids RNA Viral Medicine Infectious diseases 030211 gastroenterology & hepatology Antibody Synonymous substitution Research Article Protein Structure Sequence analysis Hepatitis C virus Science Immunology Immunoglobulins Viral diseases Viral Structure Polymorphism Single Nucleotide Microbiology 03 medical and health sciences Open Reading Frames Genetic Mutation Complementary DNA Virology medicine [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology Genetics Viral Core Humans [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Biology Immunity to Infections 030304 developmental biology Immunity RNA Proteins Hepatitis C Antibodies Molecular biology Open reading frame Macromolecular structure analysis Mutation biology.protein Nucleic Acid Conformation |
| Zdroj: | PLoS ONE PLoS ONE, Public Library of Science, 2011, 6 (1), pp.e15871. ⟨10.1371/journal.pone.0015871⟩ PLoS ONE, 2011, 6 (1), pp.e15871. ⟨10.1371/journal.pone.0015871⟩ PLoS ONE, Vol 6, Iss 1, p e15871 (2011) |
| ISSN: | 1932-6203 |
| DOI: | 10.1371/journal.pone.0015871⟩ |
| Popis: | International audience; 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. |
| Databáze: | OpenAIRE |
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