Interactions between Hepatitis C Virus and the Human Apolipoprotein H Acute Phase Protein: A Tool for a Sensitive Detection of the Virus

PLoS One. 2015 Oct 26;10(10):e0140900. doi: 10.1371/journal.pone.0140900. eCollection 2015.


The Hepatitis C virus (HCV) infection exhibits a high global prevalence frequently associated with hepatocellular carcinoma, taking years to develop. Despite the standardization of highly sensitive HCV quantitative RT-PCR (qRT-PCR) detection methods, false-negative diagnoses may be generated with current methods, mainly due to the presence of PCR inhibitors and/or low viral loads in the patient's sample. These false-negative diagnoses impact both public health systems, in developing countries, and an in lesser extent, in developed countries, including both the risk of virus transmission during organ transplantation and/or blood transfusion and the quality of the antiviral treatment monitoring. To adopt an appropriate therapeutic strategy to improve the patient's prognosis, it is urgent to increase the HCV detection sensitivity. Based upon previous studies on HBV, we worked on the capacity of the scavenger acute phase protein, Apolipoprotein H (ApoH) to interact with HCV. Using different approaches, including immunoassays, antibody-inhibition, oxidation, ultracentrifugation, electron microscopy and RT-PCR analyses, we demonstrated specific interactions between HCV particles and ApoH. Moreover, when using a two-step HCV detection process, including capture of HCV by ApoH-coated nanomagnetic beads and a home-made real-time HCV-RT-PCR, we confirmed the presence of HCV for all samples from a clinical collection of HCV-seropositive patients exhibiting an RT-PCR COBAS® TaqMan® HCV Test, v2.0 (COBAS)-positive result. In contrast, for HCV-seropositive patients with either low HCV-load as determined with COBAS or exhibiting HCV-negative COBAS results, the addition of the two-step ApoH-HCV-capture and HCV-detection process was able to increase the sensitivity of HCV detection or more interestingly, detect in a genotype sequence-independent manner, a high-proportion (44%) of HCV/RNA-positive among the COBAS HCV-negative patients. Thus, the immune interaction between ApoH and HCV could be used as a sample preparation tool to enrich and/or cleanse HCV patient's samples to enhance the detection sensitivity of HCV and therefore significantly reduce the numbers of false-negative HCV diagnosis results.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute-Phase Proteins / immunology
  • Acute-Phase Proteins / metabolism*
  • Centrifugation, Density Gradient / methods
  • False Negative Reactions
  • Hepacivirus / immunology
  • Hepacivirus / metabolism*
  • Hepatitis C / diagnosis*
  • Humans
  • Immunoenzyme Techniques / methods
  • Microscopy, Electron
  • Real-Time Polymerase Chain Reaction / methods
  • Sensitivity and Specificity
  • beta 2-Glycoprotein I / immunology
  • beta 2-Glycoprotein I / metabolism*


  • Acute-Phase Proteins
  • beta 2-Glycoprotein I

Grant support

This study was supported by a grant from the European Commission (EC) program on Lifesciences, genomics, and biotechnologies for Health, FP6-LIFESCIHEALTH-7, grant #PL037560. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. GenExpress, Immunoclin Corporations and ApoH---Technologies provided support in the form of salaries for authors MK, DB, IS, ST, and ELB but did not have any additional role in the study design, data collection and analysis, decision to publish or preparation of the manuscript. The specific roles of these authors are articulated in the 'author contributions' section.