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.
