Acute Hepatitis C Virus Structural Gene Sequences as Predictors of Persistent Viremia: Hypervariable Region 1 as a Decoy

• DOI: 10.1128/jvi.73.4.2938-2946.1999
• Publication Date: 2019-12-31T18:25:37Z
• Authors: Stuart C. Ray; Yu-Ming Wang; Oliver Laeyendecker; John R. Ticehurst; Stephen A. Villano; David L. Thomas
• Keywords: Viral quasispecies; Hypervariable region; Viremia; Nonsynonymous substitution; Seroconversion

ABSTRACT We hypothesized that hepatitis C virus (HCV) persistence is related to the sequence variability of putative envelope genes. This hypothesis was tested by characterizing quasispecies in specimens collected every six months from a cohort acutely HCV-infected subjects (mean duration specimen collection, 72 after seroconversion). evaluated 5 individuals who spontaneously cleared viremia and 10 with persistent cloning 33 1-kb amplicons spanned E1 5′ half E2, including hypervariable region 1 (HVR1). To assess complexity detect variants for sequencing, first PCR-positive sample examined using previously described method combines heteroduplex analysis single-stranded conformational polymorphisms. The ratio nonsynonymous synonymous substitutions ( d N /d S ) within each as an indicator relative selective pressure. Amino acid sequences were analyzed signature patterns, glycosylation signals, charge. Quasispecies higher ratios (selective pressure) lower those viremia; association strengthened presence combination both characteristics. In contrast, trend toward HVR1 detected among viremia. did not any such factors may affect serum HCV RNA concentration. had positive charge viremia, although no consistent motifs detected. Our data suggest associated complex immune response HVR1.