Immune Evasion Mechanisms of Hepatitis C Virus in Chronically Infected Nigerians: A Molecular Study

Hepatitis C virus (HCV) establishes chronic infection in approximately 75 percent of acutely infected individuals through sophisticated immune evasion strategies, including rapid viral quasispecies diversification, NS5A-mediated interferon signalling interference, and NK cell exhaustion. Understanding these mechanisms in the context of West African HCV genotypes, predominantly genotype 1 and 2, is important for therapeutic and vaccine development. This study characterises molecular immune evasion mechanisms in chronic HCV-infected patients at the Lagos State University Teaching Hospital, South West Nigeria. Plasma from 80 chronically infected, treatment-naive patients will be analysed for HCV quasispecies diversity in the E2 hypervariable region 1 by deep amplicon sequencing, and NS5A sequences will be screened for resistance-associated substitutions. Peripheral blood mononuclear cells will be isolated and analysed for markers of CD8 T cell exhaustion (PD-1, TIM-3, LAG-3) and NK cell phenotype by multiparametric flow cytometry. Correlations between quasispecies diversity, immune exhaustion markers, and serum HCV RNA levels will be examined. Most immune evasion studies are conducted in European or East Asian HCV genotype 1b cohorts, leaving the genotype 1a and 2 landscape prevalent in Nigeria relatively unstudied. Findings will provide mechanistic immune evasion data from a Nigerian HCV cohort, contributing to evidence for genotype-informed therapeutic strategies and potential immunotherapeutic targets. Keywords: Hepatitis C virus, immune evasion, quasispecies, T cell exhaustion, Nigeria