Evolution and function of the HCV NS3 protease in patients with acute hepatitis C and HIV coinfection

Virology. 2015 Nov:485:213-22. doi: 10.1016/j.virol.2015.06.030. Epub 2015 Aug 25.

Abstract

Little is known about the importance of the hepatitis C virus (HCV) NS3 protease in acute hepatitis C. In this prospective study, 82 consecutive patients with acute hepatitis C and human immunodeficiency virus (HIV) coinfection were enrolled. Individuals were infected with highly related HCV strains and the baseline NS3 quasispecies diversity and complexity was higher compared to a chronic hepatitis C control group (P<0.0001). Both parameters were comparable in patients with spontaneous clearance (n=6) versus treatment-induced SVR (n=5) or development of chronic hepatitis C (n=9). Longitudinal NS3 quasispecies kinetics showed a trend to a decreasing diversity and complexity (P<0.05) within 4 weeks in patients with spontaneous clearance compared to the other groups. The innate immune signalling protein CARDIF was cleaved to a similar extent independent of the outcome. Together with a more pronounced viral load decline (P<0.05), an early decreasing NS3 quasispecies evolution indicates spontaneous clearance of acute hepatitis C.

Keywords: Acute hepatitis C; CARDIF; Hepatitis C virus; Human immunodeficiency virus; NS3 protease; Quasispecies evolution; Spontaneous clearance.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adaptor Proteins, Signal Transducing / metabolism
  • Adult
  • Coinfection*
  • Evolution, Molecular*
  • Female
  • Genotype
  • HIV Infections / diagnosis
  • HIV Infections / virology*
  • Hepacivirus / genetics*
  • Hepatitis C / diagnosis
  • Hepatitis C / virology*
  • Humans
  • Male
  • Middle Aged
  • Patient Outcome Assessment
  • Phylogeny
  • Prospective Studies
  • Proteolysis
  • Reassortant Viruses / genetics
  • Viral Nonstructural Proteins / classification
  • Viral Nonstructural Proteins / genetics*
  • Viral Nonstructural Proteins / metabolism

Substances

  • Adaptor Proteins, Signal Transducing
  • MAVS protein, human
  • NS3 protein, hepatitis C virus
  • Viral Nonstructural Proteins