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Complement Regulation and Immune Evasion by Hepatitis C Virus

  • Young-Chan Kwon
  • Ranjit RayEmail author
Protocol
Part of the Methods in Molecular Biology book series (MIMB, volume 1911)

Abstract

A prominent role for complement has been identified in the linkage of innate and adaptive immunity. The liver is the main source of complement and hepatocytes are the primary sites for synthesis of complement components in vivo. We have discovered that hepatitis C virus (HCV) impairs C4 and C3 synthesis. Liver damage may diminish capacity of complement synthesis in patients. However, we observed that the changes in measured complement components in chronically HCV infected patients do not correlate with liver fibrosis or rheumatoid factor present in the blood, serum albumin, or alkaline phosphatase levels. Complement component C3 is of critical importance in B cell activation and T cell-dependent antibody responses. C3 activity is required for optimal expansion of CD8+T cells during a systemic viral infection. Deficiencies in complement may predispose patients to infections via ineffective opsonization, and defects in lytic activity via membrane attack complex. Interestingly, C9 is significantly reduced at the mRNA level in chronically HCV infected liver biopsy specimens, while many hepatocyte derived complement components (C6, C8, Factor B, MASP1, and MBL) and unrelated genes remain mostly unaffected. This implies an HCV specific effect, not a global effect from liver disease.

Key words

Hepatitis C virus Complement Cascade Convertase Opsonin Lysis siRNA Liver disease 

Notes

Acknowledgments

Our research was supported by research grants DK080812 from NIDDK, U54-AI057160 from the NIAID to the Midwest Regional center of Excellence (MRCE) for Biodefense and Emerging Infectious Diseases Research, and from the Presidential and Liver Center Research Funds of Saint Louis University.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Internal MedicineSaint Louis UniversitySt. LouisUSA
  2. 2.Department of Molecular Microbiology and ImmunologySaint Louis UniversitySt. LouisUSA
  3. 3.Institut Pasteur KoreaDaejeonRepublic of Korea

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