Genetic Diversity and Selective Pressure in Hepatitis C Virus Genotypes 1–6: Significance for Direct-Acting Antiviral Treatment and Drug Resistance

摘要: Treatment with pan-genotypic direct-acting antivirals, targeting different viral proteins, is the best option for clearing hepatitis C virus (HCV) infection in chronically infected patients. However, diversity of HCV genome a major obstacle development antiviral drugs, vaccines, and genotyping assays. In this large-scale analysis, genome-wide selective pressure was mapped, focusing on positions important treatment, drug resistance, resistance testing. A dataset 1415 full-genome sequences, including genotypes 1–6 from Los Alamos database, analyzed. 44% all positions, consensus amino acid at least one genotype. Focusing sharing same revealed that only 15% defined as highly conserved (≥99% identity) an additional 24% (≥95%). Despite its large genetic diversity, across genotypes, codon were rarely identified to be positively selected (0.23%–0.46%) predominantly found under negative pressure, suggesting mainly neutral evolution. For NS3, NS5A, NS5B, respectively, 40% (6/15), 33% (3/9), 14% (2/14) resistance-related harbored variant related potentially impeding treatment. example, NS3 80K, conferring simeprevir used treatment HCV1 patients, present 39.3% HCV1a strains 0.25% HCV1b strains. Both NS5A variants 28M 30S, known associated daclatasvir, significant proportion HCV4 (10.7%). NS5B 556G, confer non-nucleoside inhibitor dasabuvir, observed 8.4% Given sequencing efforts testing purposes may need genotype-specific or geographically tailored.