sábado, 2 de enero de 2016

Naturally occurring resistance mutations within the core and NS5B regions in Hepatitis C genotypes, particularly genotype 5a, in South Africa. - PubMed - NCBI

2015 Dec 15. pii: S0166-3542(15)30035-8. doi: 10.1016/j.antiviral.2015.11.011. [Epub ahead of print]

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

Prabdial-Sing N1, Blackard JT2, Puren AJ3, Mahomed A4, Abuelhassan W5, Mahlangu J6, Vermeulen M7, Bowyer SM8.

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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.