Deep sequencing of hepatitis C virus hypervariable region 1 reveals no correlation between genetic heterogeneity and antiviral treatment outcome View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2014-07-13

AUTHORS

Kamila Caraballo Cortés, Osvaldo Zagordi, Karol Perlejewski, Tomasz Laskus, Krzysztof Maroszek, Iwona Bukowska-Ośko, Agnieszka Pawełczyk, Rafał Płoski, Hanna Berak, Andrzej Horban, Marek Radkowski

ABSTRACT

BACKGROUND: Hypervariable region 1 (HVR1) contained within envelope protein 2 (E2) gene is the most variable part of HCV genome and its translation product is a major target for the host immune response. Variability within HVR1 may facilitate evasion of the immune response and could affect treatment outcome. The aim of the study was to analyze the impact of HVR1 heterogeneity employing sensitive ultra-deep sequencing, on the outcome of PEG-IFN-α (pegylated interferon α) and ribavirin treatment. METHODS: HVR1 sequences were amplified from pretreatment serum samples of 25 patients infected with genotype 1b HCV (12 responders and 13 non-responders) and were subjected to pyrosequencing (GS Junior, 454/Roche). Reads were corrected for sequencing error using ShoRAH software, while population reconstruction was done using three different minimal variant frequency cut-offs of 1%, 2% and 5%. Statistical analysis was done using Mann-Whitney and Fisher's exact tests. RESULTS: Complexity, Shannon entropy, nucleotide diversity per site, genetic distance and the number of genetic substitutions were not significantly different between responders and non-responders, when analyzing viral populations at any of the three frequencies (≥1%, ≥2% and ≥5%). When clonal sample was used to determine pyrosequencing error, 4% of reads were found to be incorrect and the most abundant variant was present at a frequency of 1.48%. Use of ShoRAH reduced the sequencing error to 1%, with the most abundant erroneous variant present at frequency of 0.5%. CONCLUSIONS: While deep sequencing revealed complex genetic heterogeneity of HVR1 in chronic hepatitis C patients, there was no correlation between treatment outcome and any of the analyzed quasispecies parameters. More... »

PAGES

389-389

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1471-2334-14-389

DOI

http://dx.doi.org/10.1186/1471-2334-14-389

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1053436978

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/25016390


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112 translation products
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115 ultra-deep sequencing
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117 variability
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