Mutations in carboxy-terminal part of E2 including PKR/eIF2αphosphorylation homology domain and interferon sensitivity determining region of nonstructural 5A of hepatitis C virus 1b:Their correlation with response to interferon monotherapy and viral load

AIM： To study the amino acid substitutions in the carboxy （C）-terminal part of E2 protein and in the interferon （IFN） sensitivity determining region （ISDR） and their correlation with response to IFN and viral load in 85 hepatitis C virus （HCV）-lb-infected patients treated with IFN. METHODS： The C-terminal part of E2 （codons 617-711） including PKR/eIF2α phosphorylation homology domain （PePHD） and ISDR was sequenced in 85 HCV-1b-infected patients treated by IFN monotherapy. RESULTS： The amino acid substitutions in PePHD detected only in 4 of 85 patients were not correlated either with response to iFN or with viral load. The presence of substitutions in a N-terminal variable region （codons 617-641） in the C-terminal part of E2 was significantly correlated with both small viral load （33.9% vs 13.8%, P = 0.0394） and sustained response to iFN （25.0% vs 6.9 %, P = 0.0429）. Four or more substitutions in ISDR were significantly correlated with both small viral load （78.6% vs 16.2%, P 〈 0.0001） and sustained response to iFN （85.7% vs 2.9%, P 〈 0.0001）. In multivariate analysis, ISDR in nonstructural （NS） 5A （OR = 0.39, P 〈 0.0001） and N-terminal variable region （OR = 0.51, P = 0.039） was selected as the independentpredictors for small viral load, and ISDR （OR = 39.0, P 〈 0.0001） was selected as the only independent predictor for sustained response. CONCLUSION： The N-terminal variable region in the C-terminal part of E2 correlates with both response to IFN monotherapy and viral load and is one of the factors independently associated with a small viral load.