Compartmentalization of hepatitis C virus (HCV) during HCV/HIV coinfection

Jason T Blackard1, Yoichi Hiasa, Laura Smeaton

  • 1Division of Digestive Diseases, University of Cincinnati College of Medicine, Cincinnati, OH 45267, and Gastrointestinal Unit, Massachusetts General Hospital, Boston, USA. jason.blackard@uc.edu

Insights

Hepatitis C virus (HCV) replicates differently in blood cells and serum, especially in coinfection with HIV. Specific amino acid changes in HCV within blood cells may impact treatment response.

Area of Science:

  • Virology
  • Immunology
  • Infectious Diseases

Background:

  • Extrahepatic replication of Hepatitis C virus (HCV) is crucial for its transmission and treatment outcomes.
  • Understanding HCV diversity in different body compartments is essential for managing the infection.

Purpose of the Study:

  • To investigate distinct amino acid signatures of HCV replicating in peripheral blood mononuclear cells (PBMCs).
  • To compare HCV diversity in serum and PBMCs during HCV monoinfection and HCV/HIV coinfection.

Main Methods:

  • Analysis of longitudinal HCV E1-HVR1 sequences from serum and PBMCs.
  • Comparison of genetic distances and sequence identity between compartments.
  • Identification of PBMC-specific amino acid signatures.

Main Results:

  • Higher serum genetic distances were observed in HCV/HIV-coinfected individuals.
  • HCV sequences in serum and PBMCs frequently diverged, indicating compartmentalization.
  • PBMC-specific amino acid signatures were identified in all coinfected participants.

Conclusions:

  • HCV demonstrates compartmentalization and distinct amino acid profiles in PBMCs, particularly during HIV coinfection.
  • These extrahepatic HCV variations may influence treatment efficacy and warrant further investigation.

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