Humoral immune system targets clonotypic antibody-associated hepatitis C virus
| Autor: | Elizabeth Kenny-Walsh, Orla Crosbie, Amruta S. Naik, Brendan A. Palmer, Liam J. Fanning |
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| Rok vydání: | 2017 |
| Předmět: |
Serum
0301 basic medicine viruses Hepatitis C virus Hepacivirus Viral quasispecies Biology medicine.disease_cause Virus Neutralization Epitope Immunoglobulin Fab Fragments Viral Proteins 03 medical and health sciences Viral Envelope Proteins Neutralization Tests Virology medicine Humans Amino Acid Sequence Viremia Infectivity virus diseases Hepatitis C Antibodies Hepatitis C Chronic digestive system diseases Immunity Humoral 030104 developmental biology Epitope mapping Immunology biology.protein Endopeptidase K Antibody Epitope Mapping |
| Zdroj: | Journal of General Virology. 98:179-189 |
| ISSN: | 1465-2099 0022-1317 |
| DOI: | 10.1099/jgv.0.000659 |
| Popis: | Hypervariable region 1 (HVR1) is one of the potential neutralization domains in the E2 glycoprotein of hepatitis C virus (HCV). Point mutations of the HVR1 can lead to humoral immune escape in HCV-infected patients. In this study, we segregated the chronically infected viraemic sera from HCV-infected patients into populations of antibody-free virus and antibody-associated virus (AAV) and mapped potential epitopes within the E1E2 gene junction of AAV sequences (residues 364-430). Furthermore, we generated HCV pseudoparticles (HCVpp) derived from AAV sequences to assess their infectivity. We studied the neutralization potential of virus-free Fab obtained from antibody-virus complexes, in the HCVpp system. We observed selective targeting of clonotypic HCV variants from the quasispecies pool. Moreover, we identified potential neutralizing epitopes within the HVR1 and an additional epitope that overlapped with a broadly neutralizing AP33 epitope (amino acid 412-423 in E2). We observed a marked difference in the infectivity of HCVpp generated using E1E2 sequences isolated from AAV. We document reduction in the infectivity of HCVpp-H77 and HCVpp derived from AAV sequences when challenged with virus-free Fab. Our results provide novel insights into the complexities of engagement between HCV and the humoral immune system. |
| Databáze: | OpenAIRE |
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