HCV Genotype Distribution and Molecular Characteristics of HCV Core Domain I in Persons Living with HIV and HCV from Yunnan Province, China

Yunnan Province, a critical southwestern Chinese border region and gateway to Southeast Asia, faces a complex human immunodeficiency virus (HIV)/hepatitis C virus (HCV) co-infection epidemic. Molecular data on HCV Core domain I in persons living with HIV and HCV (PLWHH) remain scarce here. This study addresses this gap by analyzing prevalent HCV strains, identifying amino acid mutations, and predicting immune epitopes and structural motifs to inform clinical and vaccine strategies. The serum samples from 128 PLWHH, which were collected across 14 cities in Yunnan Province between January 2019 and September 2021, were analyzed. RNA was extracted from these samples, and complementary DNA was subsequently synthesized. PCR amplification of the HCV Core domain I was performed using genotype-specific primers, followed by sequencing. Bioinformatics tools were used for phylogenetic analysis, amino acid mutation analysis, and the prediction of B-cell and T-cell epitopes, as well as N-glycosylation sites. In addition, secondary and tertiary structure modeling was carried out. HCV genotypes included 1a (<i>n</i> = 3), 1b (<i>n</i> = 23), 3a (<i>n</i> = 29), 3b (<i>n</i> = 51), 6a (<i>n</i> = 4), 6n (<i>n</i> = 15), and 6xa (<i>n</i> = 3). Eleven mutations were identified in Core domain I, with R70Q (41.4%, <i>n</i> = 53) and R70P (14.06%, <i>n</i> = 18) linked to severe disease progression. B-cell epitope analysis revealed three antigenic sites in genotypes 1/3 and four in genotype 6. T-cell epitope prediction identified two antigenic sites across genotypes 1/3/6, but no cytotoxic T-cell epitopes or N-glycosylation sites were detected. Structural modeling showed Core domain I in genotypes 1/3/6 comprised helices, sheets, turns, and coils (coils predominant), with significant structural variations between genotypes. In the PLWHH in Yunnan, HCV exhibits diverse epidemiological characteristics. Multiple amino acid mutations in Core domain I, often linked to severe disease outcomes, are frequently observed. This region also contains several immune-related antigenic epitopes. In addition, variations in the secondary and tertiary structures of Core domain I differ across genotypes.