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Sequence heterogeneity of NS5A and core proteins of hepatitis C virus and virological responses to pegylated-interferon/ribavirin combination therapy.
Microbiol Immunol. 2011 Jun; 55(6):418-26.MI

Abstract

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.

Authors+Show Affiliations

Division of Microbiology, Center for Infectious Diseases, Kobe University Graduate School of Medicine, Kobe, Japan.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21371092

Citation

El-Shamy, Ahmed, et al. "Sequence Heterogeneity of NS5A and Core Proteins of Hepatitis C Virus and Virological Responses to Pegylated-interferon/ribavirin Combination Therapy." Microbiology and Immunology, vol. 55, no. 6, 2011, pp. 418-26.
El-Shamy A, Shoji I, Saito T, et al. Sequence heterogeneity of NS5A and core proteins of hepatitis C virus and virological responses to pegylated-interferon/ribavirin combination therapy. Microbiol Immunol. 2011;55(6):418-26.
El-Shamy, A., Shoji, I., Saito, T., Watanabe, H., Ide, Y. H., Deng, L., Kawata, S., & Hotta, H. (2011). Sequence heterogeneity of NS5A and core proteins of hepatitis C virus and virological responses to pegylated-interferon/ribavirin combination therapy. Microbiology and Immunology, 55(6), 418-26. https://doi.org/10.1111/j.1348-0421.2011.00331.x
El-Shamy A, et al. Sequence Heterogeneity of NS5A and Core Proteins of Hepatitis C Virus and Virological Responses to Pegylated-interferon/ribavirin Combination Therapy. Microbiol Immunol. 2011;55(6):418-26. PubMed PMID: 21371092.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sequence heterogeneity of NS5A and core proteins of hepatitis C virus and virological responses to pegylated-interferon/ribavirin combination therapy. AU - El-Shamy,Ahmed, AU - Shoji,Ikuo, AU - Saito,Takafumi, AU - Watanabe,Hisayoshi, AU - Ide,Yoshi-Hiro, AU - Deng,Lin, AU - Kawata,Sumio, AU - Hotta,Hak, PY - 2011/3/5/entrez PY - 2011/3/5/pubmed PY - 2011/9/14/medline SP - 418 EP - 26 JF - Microbiology and immunology JO - Microbiol. Immunol. VL - 55 IS - 6 N2 - 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. SN - 1348-0421 UR - https://www.unboundmedicine.com/medline/citation/21371092/Sequence_heterogeneity_of_NS5A_and_core_proteins_of_hepatitis_C_virus_and_virological_responses_to_pegylated_interferon/ribavirin_combination_therapy_ L2 - https://doi.org/10.1111/j.1348-0421.2011.00331.x DB - PRIME DP - Unbound Medicine ER -