Author: Izquierdo, Laure; Oliveira, Catarina; Fournier, Carole; Descamps, Véronique; Morel, Virginie; Dubuisson, Jean; Brochot, Etienne; Francois, Catherine; Castelain, Sandrine; Duverlie, Gilles; Helle, Francois
Title: Hepatitis C Virus Resistance to Carbohydrate-Binding Agents Document date: 2016_2_12
ID: 1a4l1beo_31
Snippet: In order to determine whether the mutations selected upon lectin exposure confer resistance to the lectins, we performed dose response curves and compared the ability of the lectins to inhibit WT HCVcc and the mutants containing the combinations of three mutations. As shown in Fig 5, we observed that the combinations of three mutations V284A-V392D-S449P, M338V-L612M-L755M, M338V-N417S-L755M and M338V-A400D-L755M did not confer any resistance to .....
Document: In order to determine whether the mutations selected upon lectin exposure confer resistance to the lectins, we performed dose response curves and compared the ability of the lectins to inhibit WT HCVcc and the mutants containing the combinations of three mutations. As shown in Fig 5, we observed that the combinations of three mutations V284A-V392D-S449P, M338V-L612M-L755M, M338V-N417S-L755M and M338V-A400D-L755M did not confer any resistance to the lectin they have been selected with (GNA, CV-N, ConA and GRFT, respectively). We also analyzed the effect of simple mutation and combination of two mutations on the sensitivity to inhibition by lectins. In the same way, we did not evidence any resistance conferred by the mutations selected upon GNA, CV-N or ConA exposure, alone or in combination of two (S3 Fig). The results obtained with A400D, M338V-A400D and A400D-L755M mutants were surprising since at low concentrations of GRFT (between 0.03 μg/mL and 0.3 μg/mL), the We also tested the sensitivity of the four triple mutants to inhibition by other lectins and observed that they were equally sensitive to CV-N, ConA and GRFT (Figs 5B and 4C and 4D) . In contrast, we noticed that mutants M338V-N417S-L755M, M338V-L612M-L755M and M338V-A400D-L755M were more sensitive to GNA inhibition (Fig 5A) . These combinations of mutations led to a 9.8-, 7.3-and 2.3-fold reduction in the effective concentration required for half-maximal inhibition as compared to WT, respectively.
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