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Sequence heterogeneity of NS5A and core proteins of hepatitis C virus and virological responses to pegylated‐interferon/ribavirin combination therapy
Author(s) -
ElShamy Ahmed,
Shoji Ikuo,
Saito Takafumi,
Watanabe Hisayoshi,
Ide YoshiHiro,
Deng Lin,
Kawata Sumio,
Hotta Hak
Publication year - 2011
Publication title -
microbiology and immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.664
H-Index - 70
eISSN - 1348-0421
pISSN - 0385-5600
DOI - 10.1111/j.1348-0421.2011.00331.x
Subject(s) - ns5a , ribavirin , virology , pegylated interferon , hepatitis c virus , biology , interferon , virus , hepacivirus , viral load , alpha interferon
Both host and viral factors have been implicated in influencing the response to pegylated‐interferon/ribavirin (PEG‐IFN/RBV) therapy for hepatitis C virus (HCV) infection. Among the viral factors, sequence heterogeneity within NS5A and core regions has been proposed. This study aimed to clarify the relationship between virological responses to PEG‐IFN/RBV therapy and sequence heterogeneity within NS5A, including the IFN/RBV resistance‐determining region (IRRDR), the interferon sensitivity‐determining region (ISDR) and the core region. Pretreatment sequences of NS5A and the core regions were analyzed in 57 HCV‐1b‐infected patients who were to be treated with PEG‐IFN/RBV. Of 40 patients infected with HCV having an IRRDR with four or more mutations (IRRDR ≥ 4), 28 (70%) patients achieved a sustained virological response (SVR). On the other hand, only 4 (24%) of 17 patients infected with HCV having an IRRDR with three or fewer mutations (IRRDR ≤ 3) achieved a SVR ( P = 0.001). Similarly, 22 (71%) of 31 patients infected with HCV and having an ISDR with one or more mutations (ISDR ≥ 1) achieved a SVR while 10 (38%) of 26 patients infected with HCV and having an ISDR without any mutations (ISDR = 0) achieved a SVR ( P = 0.014). As for the core region, there was significant correlation between a single mutation at position 70 (Gln 70 ) and non‐SVR ( P = 0.02). Notably, Gln 70 was more prominently associated with the null response ( P = 0.0007). In conclusion, sequence heterogeneity within the IRRDR and ISDR, and a single point mutation at position 70 of the core region of HCV‐1b are likely to be correlated with virological responses to PEG‐IFN/RBV therapy.