Development of an effective single-chain variable fragment recognizing a novel epitope in the hepatitis C virus E2 protein that restricts virus entry into hepatocytes

Previously, we reported a neutralizing monoclonal antibody, A8A11, raised against a novel conserved epitope within the hepatitis C virus (HCV) E2 protein, that could significantly reduce HCV replication. Here, we report the nucleotide sequence of A8A11 and demonstrate the efficacy of a single-chain...

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Bibliographic Details
Published in:Archives of virology 2024-05, Vol.169 (5), p.112-112, Article 112
Main Authors: Das, Soma, Behera, Padmanava, Shewale, Dipeshwari J, Bodele, Janhavi, Das, Saumitra, Karande, Anjali A
Format: Article
Language:English
Subjects:
Animals
Antibodies, Monoclonal - immunology
Antibodies, Neutralizing - immunology
Biomedical and Life Sciences
Biomedicine
Brief Report
Cell culture
Cloning
E2 protein
Epitopes
Epitopes - immunology
Hepacivirus - genetics
Hepacivirus - immunology
Hepacivirus - physiology
Hepatitis C
Hepatitis C - immunology
Hepatitis C - virology
Hepatocytes
Hepatocytes - immunology
Hepatocytes - virology
Humans
Infections
Infectious Diseases
Light
Medical Microbiology
Mice
Monoclonal antibodies
Nucleotide sequence
Peptides
Proteins
Replication
Single-Chain Antibodies - genetics
Single-Chain Antibodies - immunology
Therapeutic applications
Vaccines
Viral Envelope Proteins - genetics
Viral Envelope Proteins - immunology
Viral Envelope Proteins - metabolism
Virology
Virus Internalization
Virus Replication
Virus-like particles
Viruses
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Description
Summary:Previously, we reported a neutralizing monoclonal antibody, A8A11, raised against a novel conserved epitope within the hepatitis C virus (HCV) E2 protein, that could significantly reduce HCV replication. Here, we report the nucleotide sequence of A8A11 and demonstrate the efficacy of a single-chain variable fragment (scFv) protein that mimics the antibody, inhibits the binding of an HCV virus-like particle to hepatocytes, and reduces viral RNA replication in a cell culture system. More importantly, scFv A8A11 was found to effectively restrict the increase of viral RNA levels in the serum of HCV-infected chimeric mice harbouring human hepatocytes. These results suggest a promising approach to neutralizing-antibody-based therapeutic interventions against HCV infection.
ISSN:0304-8608
1432-8798
DOI:10.1007/s00705-024-06024-4