Details

Autor(en) / Beteiligte

• Prabdial-Sing, N.
• Blackard, J.T.
• Puren, A.J.
• Mahomed, A.
• Abuelhassan, W.
• Mahlangu, J.
• Vermeulen, M.
• Bowyer, S.M.

Titel

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

Ist Teil von

• Antiviral research, 2016-03, Vol.127, p.90-98

Ort / Verlag

Netherlands: Elsevier B.V

Erscheinungsjahr

2016

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. •We examined mutational changes of hepatitis C in the core/E1 and NS5B genes.•Phylogenetic analyses were performed using Bayesian inferences.•Diversity within known CD4+ and CD8+ T-cell epitopes was also explored.•Mutations, associated with interferon resistance, were present in genotype 5a samples at baseline.