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• W2055369221 abstract "Background/Aims The hepatitis C virus NS5A protein is phosphorylated by several cellular kinases, including casein kinase 2 (CK2). Little is known about CK2 phosphorylation of NS5A from different HCV genotypes and clinical isolates. Methods NS5A from patients with HCV-1a (24 cases), HCV-1b (9) or HCV-3 (16) was analyzed by direct sequencing and CK2 phosphorylation sites were defined using a well-validated prediction rule. In vitro phosphorylation assays were performed using recombinant CK2 and synthetic peptides or full-length NS5A. In vivo phosphorylation by endogenous CK2 of NS5A expressed in hepatoma cells was also investigated. Results The mean number of CK2 sites within full-length NS5A, was significantly higher in HCV-3 compared to HCV-1a (P < 0.01) and HCV-1b (P < 0.01). The number of CK2 sites was more homogeneous in HCV-3 variants compared to HCV-1a and HCV-1b variants (P < 0.05). The number of predicted CK2 sites correlated with the degree of in vitro and in vivo phosphorylation of NS5A by CK2. Conclusions CK2-dependent phosphorylation of NS5A is heterogeneous among different HCV genotypes and clinical isolates. This might have an influence on virus biology and pathogenicity. The hepatitis C virus NS5A protein is phosphorylated by several cellular kinases, including casein kinase 2 (CK2). Little is known about CK2 phosphorylation of NS5A from different HCV genotypes and clinical isolates. NS5A from patients with HCV-1a (24 cases), HCV-1b (9) or HCV-3 (16) was analyzed by direct sequencing and CK2 phosphorylation sites were defined using a well-validated prediction rule. In vitro phosphorylation assays were performed using recombinant CK2 and synthetic peptides or full-length NS5A. In vivo phosphorylation by endogenous CK2 of NS5A expressed in hepatoma cells was also investigated. The mean number of CK2 sites within full-length NS5A, was significantly higher in HCV-3 compared to HCV-1a (P < 0.01) and HCV-1b (P < 0.01). The number of CK2 sites was more homogeneous in HCV-3 variants compared to HCV-1a and HCV-1b variants (P < 0.05). The number of predicted CK2 sites correlated with the degree of in vitro and in vivo phosphorylation of NS5A by CK2. CK2-dependent phosphorylation of NS5A is heterogeneous among different HCV genotypes and clinical isolates. This might have an influence on virus biology and pathogenicity." @default.
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• W2055369221 date "2007-12-01" @default.
• W2055369221 modified "2023-10-14" @default.
• W2055369221 title "Heterogeneity of CK2 phosphorylation sites in the NS5A protein of different hepatitis C virus genotypes" @default.
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• W2055369221 doi "https://doi.org/10.1016/j.jhep.2007.07.020" @default.
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