Net emergence of substitutions at position 28 in NS5A of hepatitis C virus genotype 4 in patients failing direct-acting antivirals detected by next-generation sequencing
| العنوان: | Net emergence of substitutions at position 28 in NS5A of hepatitis C virus genotype 4 in patients failing direct-acting antivirals detected by next-generation sequencing |
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| المؤلفون: | Anne Simon, Eve Todesco, Luminita Bonyhay, Vincent Calvez, Thuy Van Nguyen, Thierry Poynard, Fabienne Caby, Anne Gervais, Lucile Larrouy, Yvon Calmus, Marc-Antoine Valantin, Anne-Geneviève Marcelin, Pascal Lebray, Sepideh Akhavan |
| المساهمون: | Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Infection, Anti-microbiens, Modélisation, Evolution (IAME (UMR_S_1137 / U1137)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU) |
| المصدر: | International Journal of Antimicrobial Agents International Journal of Antimicrobial Agents, 2019, 53, pp.80-83. ⟨10.1016/j.ijantimicag.2018.09.010⟩ |
| بيانات النشر: | Elsevier BV, 2019. |
| سنة النشر: | 2019 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Microbiology (medical), Genotype, [SDV]Life Sciences [q-bio], viruses, Hepacivirus, Hepatitis C virus, 030106 microbiology, Viral Nonstructural Proteins, medicine.disease_cause, Antiviral Agents, DNA sequencing, Virus, 03 medical and health sciences, chemistry.chemical_compound, symbols.namesake, 0302 clinical medicine, Drug Resistance, Viral, medicine, Humans, Pharmacology (medical), Treatment Failure, 030212 general & internal medicine, NS5B, Sanger sequencing, biology, High-Throughput Nucleotide Sequencing, virus diseases, General Medicine, Nucleic acid amplification technique, Middle Aged, biology.organism_classification, Hepatitis C, Virology, digestive system diseases, 3. Good health, Infectious Diseases, Amino Acid Substitution, chemistry, symbols, Female, Nucleic Acid Amplification Techniques |
| الوصف: | More data on resistance of HCV genotype (GT) 3 and 4 to direct-acting antivirals (DAAs) are still needed. Here we investigated the presence of resistance-associated substitutions (RASs) pre- and post-treatment and their emergence under DAAs in HCV GT3- and GT4-infected patients failing DAA regimens by next-generation sequencing (NGS). Sanger sequencing and NGS were performed on NS5B and NS5A in plasma samples prior to and post treatment of 13 patients. Positions implicated in resistance to anti-NS5A and anti-NS5B in the literature were analysed. No baseline RASs was detected in NS5B but one GT4r virus developed the mutation S282T at failure. In NS5A, pre-existing RASs or polymorphisms were detected in viruses of 6/10 patients (L28M for a GT4a, M28V for a GT4r, L30R for a GT4a, 2 GT4d and 1 GT4r, and T58P for a GT4d) by Sanger sequencing and in viruses of 7/10 patients by NGS. Additional baseline minority substitutions detected by NGS were Y93H in a GT3a, L28M in a GT4a and GT4d, and L28F in a GT4d virus. At failure, these substitutions were found at a frequency of 100%. Y93H was detected alone at baseline, whilst L28M and L28F were accompanied by polymorphisms L30R or L30R + T58P. Use of NGS in patients failing DAAs and infected by HCV GT3 and GT4 revealed the emergence of specific patterns of substitutions in NS5A and NS5B, in particular substitutions at position 28 in NS5A in GT4 virus, highlighting the need to list these substitutions in guidelines for resistance interpretation. |
| تدمد: | 0924-8579 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dda7c62792e1e83747aab21b5a879298Test https://doi.org/10.1016/j.ijantimicag.2018.09.010Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....dda7c62792e1e83747aab21b5a879298 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 09248579 |
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