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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
Sequence heterogeneity in NS5A of hepatitis C virus genotypes 2a and 2b and clinical outcome of Pegylated-Interferon/ribavirin therapy
PLoS ONE, Volume 7, No. 2, Article e30513, Year 2012
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Description
Pegylated-interferon plus ribavirin (PEG-IFN/RBV) therapy is a current standard treatment for chronic hepatitis C. We previously reported that the viral sequence heterogeneity of part of NS5A, referred to as the IFN/RBV resistance-determining region (IRRDR), and a mutation at position 70 of the core protein of hepatitis C virus genotype 1b (HCV-1b) are significantly correlated with the outcome of PEG-IFN/RBV treatment. Here, we aimed to investigate the impact of viral genetic variations within the NS5A and core regions of other genotypes, HCV-2a and HCV-2b, on PEG-IFN/RBV treatment outcome. Pretreatment sequences of NS5A and core regions were analyzed in 112 patients infected with HCV-2a or HCV-2b, who were treated with PEG-IFN/RBV for 24 weeks and followed up for another 24 weeks. The results demonstrated that HCV-2a isolates with 4 or more mutations in IRRDR (IRRDR[2a]≥4) was significantly associated with rapid virological response at week 4 (RVR) and sustained virological response (SVR). Also, another region of NS5A that corresponds to part of the IFN sensitivity-determining region (ISDR) plus its carboxy-flanking region, which we referred to as ISDR/+C[2a], was significantly associated with SVR in patients infected with HCV-2a. Multivariate analysis revealed that IRRDR[2a]≥4 was the only independent predictive factor for SVR. As for HCV-2b infection, an N-terminal half of IRRDR having two or more mutations (IRRDR[2b]/N≥2) was significantly associated with RVR, but not with SVR. No significant correlation was observed between core protein polymorphism and PEG-IFN/RBV treatment outcome in HCV-2a or HCV-2b infection.
Conclusion:
The present results suggest that sequence heterogeneity of NS5A of HCV-2a (IRRDR[2a]≥4 and ISDR/+C[2a]), and that of HCV-2b (IRRDR[2b]/N≥2) to a lesser extent, is involved in determining the viral sensitivity to PEG-IFN/RBV therapy. © 2012 El-Shamy et al.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3271109/bin/pone.0030513.s001.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3271109/bin/pone.0030513.s002.tif
https://efashare.b-cdn.net/share/pmc/articles/PMC3271109/bin/pone.0030513.s003.doc
https://efashare.b-cdn.net/share/pmc/articles/PMC3271109/bin/pone.0030513.s004.doc
Authors & Co-Authors
El-Shamy, Ahmed M.
Japan, Kobe
Graduate School of Medicine
Egypt, Ismailia
Faculty of Veterinary Medicine
Shoji, Ikuo
Japan, Kobe
Graduate School of Medicine
Kim, Sooryang
Japan, Kobe
Kobe Asahi Hospital
Ide, Yoshihiro
Japan, Kobe
Graduate School of Medicine
Imoto, Susumu
Japan, Kobe
Kobe Asahi Hospital
Deng, Lin
Japan, Kobe
Graduate School of Medicine
Yoon, Seitetsu
Japan, Kakogawa
Hyogo Prefectural Kakogawa Medical Center
Fujisawa, Takashi
Japan, Himeji
Ironworks Memorial Hirohata Hospital
Tani, Satoshi
Japan, Kobe
Konan Hospital
Yano, Yoshihiko
Japan, Kobe
Graduate School of Medicine
Seo, Yasushi
Japan, Kobe
Graduate School of Medicine
Azuma, Takeshi
Japan, Kobe
Graduate School of Medicine
Hotta, Haku
Japan, Kobe
Graduate School of Medicine
Statistics
Citations: 21
Authors: 13
Affiliations: 6
Identifiers
Doi:
10.1371/journal.pone.0030513
e-ISSN:
19326203
Research Areas
Cancer
Genetics And Genomics
Infectious Diseases