Cellular activation and intracellular HCV load in peripheral blood monocytes isolated from HCV monoinfected and HIV-HCV coinfected patients

Isabelle Dichamp; Wasim Abbas; Amit Kumar; Vincent Di Martino; Georges Herbein

doi:10.1371/journal.pone.0096907

Cellular activation and intracellular HCV load in peripheral blood monocytes isolated from HCV monoinfected and HIV-HCV coinfected patients

PLoS One. 2014 May 8;9(5):e96907. doi: 10.1371/journal.pone.0096907. eCollection 2014.

Authors

Isabelle Dichamp¹, Wasim Abbas¹, Amit Kumar¹, Vincent Di Martino², Georges Herbein¹

Affiliations

¹ Pathogens and Inflammation Department, UPRES EA4266, SFR FED 4234, University of Franche-Comté, Besancon, France; Department of Virology, CHRU Besançon, Besançon, France.
² Pathogens and Inflammation Department, UPRES EA4266, SFR FED 4234, University of Franche-Comté, Besancon, France; Department of Hepatology, CHRU Besançon, Besançon, France.

Abstract

Background: During HCV infection, the activation status of peripheral blood monocytes and its impact on HCV replication are poorly understood. We hypothesized that a modified activation of peripheral blood monocytes in HIV-HCV coinfected compared to HCV monoinfected patients may contribute to different monocytes reservoirs of HCV replication.

Methods: We performed a case-control analysis involving HCV-infected patients with and without HIV coinfection. In peripheral blood mononuclear cells (PBMCs), peripheral blood lymphocytes (PBLs) and peripheral blood monocytes isolated from HCV monoinfected and HIV-HCV coinfected patients, intracellular HCV load and a marker of cellular activation, nuclear factor-kappaB (NF-κB) activation, were quantified using intracellular detection of HCV-core protein and electrophoretic mobility shift assay, respectively.

Results: Intracellular HCV loads were higher in monocytes isolated from HIV-HCV coinfected patients than in those of monoinfected patients. Among PBMCs isolated from HIV-HCV coinfected patients, intracellular HCV loads were higher in monocytes compared to PBLs. Cellular activation as measured by NF-κB activation was higher in monocytes isolated from HIV-HCV coinfected patients than in those of monoinfected patients.

Conclusions: Our results reveal the peripheral blood monocytes as an important extrahepatic reservoir for HCV in HIV-HCV coinfected patients and indicate a potential association between the activation state of monocytes and the size of the HCV reservoir in HIV-HCV coinfected patients.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adult
Aged
Coinfection*
Female
HIV Infections / complications*
Hepacivirus / physiology*
Hepatitis C / blood
Hepatitis C / complications*
Humans
Intracellular Space / virology*
Male
Middle Aged
Monocytes / cytology*
Monocytes / metabolism
Monocytes / virology
NF-kappa B / metabolism
Viral Load*

Substances

NF-kappa B

Grants and funding

This work was supported by grants to G.H. from the University of Franche-Comté (UFC) and the Région Franche-Comté (RECH-FON12-000013). W.A. is a recipient of a doctoral scholarship from the Higher Education Commission, Pakistan. A.K. is a recipient of a postdoctoral fellowship of the Region Franche-Comté (2012C-06102). The authors thank Diasorin SA for its financial support. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.