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Published on: July 16, 2012
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.
Abstract:
Extrahepatic replication has important implications for the transmission and treatment of hepatitis C virus (HCV). We analyzed longitudinal HCV diversity in peripheral-blood mononuclear cells (PBMCs) and serum during HCV monoinfection and HCV/HIV coinfection to determine whether distinct amino acid signatures characterized HCV replicating within PBMCs. Analysis of E1-HVR1 sequences demonstrated higher serum genetic distances among HCV/human immunodeficiency virus (HIV)-coinfected persons. Moreover, consensus PBMC sequences were rarely identical to those in the corresponding serum, suggesting divergence in these 2 compartments. Three of 5 HCV/HIV-coinfected participants showed evidence of HCV compartmentalization in PBMCs. Additionally, signature sequence analysis identified PBMC-specific amino acids in all HCV/HIV-coinfected persons. To our knowledge, this is the first study to identify specific amino acids that may distinguish HCV variants replicating in PBMCs. It is provocative to speculate that extrahepatic HCV diversity may be an important determinant of treatment response and thus warrants additional study, particularly during HCV/HIV coinfection.
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