Naturally occurring resistance mutations within the core and NS5B regions in hepatitis C genotypes, particularly genotype 5a, in South Africa

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dc.contributor.author Prabdial-Sing, N.
dc.contributor.author Blackard, J.T.
dc.contributor.author Puren, A.J.
dc.contributor.author Mahomed, A.
dc.contributor.author Abuelhassan, W.
dc.contributor.author Mahlangu, J.
dc.contributor.author Vermeulen, M.
dc.contributor.author Bowyer, Sheila Mary
dc.date.accessioned 2016-08-04T10:59:02Z
dc.date.issued 2016-03
dc.description.abstract Approximately 1 million South Africans are infected with Hepatitis C virus (HCV). The standard of care (SOC) in South Africa is combination therapy (pegylated interferon and ribavirin). HCV genotypes and/or mutations in the core/ non-structural regions have been associated with response to therapy and/or disease progression. This study examines mutations in the core (29-280 amino acids, including ~90 E1 amino acids) and NS5B (241-306 amino acids) regions on pre-treatment isolates from patients attending Johannesburg hospitals or asymptomatic South African blood donors. Diversity within known CD4+ and CD8+ T-cell epitopes was also explored. Samples grouped into subtypes 1a (N=10) 1b (N=12), 3a(N=5), 4a (N=3) and 5a(N=61). Two mutations, associated with interferon resistance–R70Q and T110N–were present in 29 genotype 5a core sequences. No resistance mutation to NS5B nucleotide inhibitors, sofosbuvir was found. Six putative CD8+ and one CD4+ T-cell epitope sequence in the core region showed binding scores of <300 IC50nM to HLA alleles frequently observed in the South African population. No known CD8+ and CD4+ T-cell epitopes were mapped in the NS5B region. The analysis begs the question whether those infected with genotype 5a will benefit better on interferon-free combination therapies. This study provides new insight into one of the lesser studied HCV genotypes and compares the diversity seen in a large pre-treatment cohort with other subtypes. en_ZA
dc.description.department Medical Virology en_ZA
dc.description.embargo 2017-03-31
dc.description.librarian hb2016 en_ZA
dc.description.sponsorship Poliomyelitis Research Foundation, grant 95097. en_ZA
dc.description.uri http://www.elsevier.com/locate/antiviral en_ZA
dc.identifier.citation Prabdial-Sing, N, Blackard, JT, Puren, AJ, Mahomed, A, Abuelhassan, W, Mahlangu, J, Vermeulen, M & Bowyer, SM 2016, 'Naturally occurring resistance mutations within the core and NS5B regions in hepatitis C genotypes, particularly genotype 5a, in South Africa', Antiviral Research, vol. 127, pp. 90-98. en_ZA
dc.identifier.issn 0166-3542 (print)
dc.identifier.issn 1872-9096 (online)
dc.identifier.other 10.1016/j.antiviral.2015.11.011
dc.identifier.uri http://hdl.handle.net/2263/56195
dc.language.iso en en_ZA
dc.publisher Elsevier en_ZA
dc.rights © 2015 Elsevier B.V. All rights reserved. Notice : this is the author’s version of a work that was accepted for publication in Antiviral Research. Changes resulting from the publishing process, such as peer review, editing, corrections, structural formatting, and other quality control mechanisms may not be reflected in this document. Changes may have been made to this work since it was submitted for publication. A definitive version was subsequently published in Antiviral Research, vol. 127, pp. 90-98, 2016. doi : 10.1016/j.antiviral.2015.11.011. en_ZA
dc.subject Genotype 5 en_ZA
dc.subject Interferon en_ZA
dc.subject Mutations en_ZA
dc.subject Therapy en_ZA
dc.subject Hepatitis C virus (HCV) en_ZA
dc.subject Standard of care (SOC) en_ZA
dc.title Naturally occurring resistance mutations within the core and NS5B regions in hepatitis C genotypes, particularly genotype 5a, in South Africa en_ZA
dc.type Postprint Article en_ZA


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