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Published on: May 10, 2022
Hepatitis C Virus Resistance to Carbohydrate-Binding Agents
Laure Izquierdo1, Catarina Oliveira1, Carole Fournier1
1EA4294, Laboratoire de Virologie, Centre Universitaire de Recherche en Santé, Centre Hospitalier Universitaire et Université de Picardie Jules Verne, Amiens, France.
Carbohydrate binding agents (CBAs) show potential against viruses like Hepatitis C Virus (HCV). This study found HCV does not develop direct resistance to CBAs via envelope mutations, suggesting indirect resistance mechanisms.
Area of Science:
- Virology
- Immunology
- Biochemistry
Background:
- Carbohydrate binding agents (CBAs), including natural lectins, are explored as broad-spectrum antivirals targeting viral envelope N-glycans.
- Previous studies show CBAs can select for Human Immunodeficiency Virus (HIV) mutants with deletions in N-glycosylation sites, increasing antibody sensitivity.
Purpose of the Study:
- To investigate the in vitro resistance of Hepatitis C Virus (HCV) to CBAs.
- To identify potential mutations conferring resistance and assess their impact on viral fitness and sensitivity to inhibitors.
Main Methods:
- HCV was cultured with increasing concentrations of Galanthus nivalis agglutinin (GNA), Cyanovirin-N, Concanavalin-A, and Griffithsin for over eight weeks.
- Isolated viral strains were sequenced to identify mutations in envelope glycoproteins (E1E2) and other proteins.
- The impact of identified mutations on CBA sensitivity, viral fitness, and neutralization by antibodies (3/11) or soluble CD81 was evaluated.
Main Results:
- No mutations in HCV envelope glycoproteins directly conferred resistance to CBAs.
- Some identified mutations increased sensitivity to the 3/11 neutralizing antibody and soluble CD81-LEL.
- Mutations were also found in HCV Core and non-structural proteins.
Conclusions:
- HCV resistance to CBAs appears not to be mediated by direct mutations in envelope genes, unlike HIV.
- Indirect resistance mechanisms involving mutations in other viral proteins are suggested for HCV.
- Further research is required to fully understand the mechanisms of HCV resistance to CBAs.
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