Sequence Heterogeneity in NS5A of Hepatitis C Virus Genotypes 2a and 2b and Clinical Outcome of Pegylated-Interferon/Ribavirin Therapy

被引：16

作者：

El-Shamy, Ahmed ^{[1
,2
]}

Shoji, Ikuo ^{[1
]}

Kim, Soo-Ryang ^{[3
]}

Ide, Yoshihiro ^{[1
]}

Imoto, Susumu ^{[3
]}

Deng, Lin ^{[1
]}

Yoon, Seitetsu ^{[4
]}

Fujisawa, Takashi ^{[5
]}

Tani, Satoshi ^{[6
]}

Yano, Yoshihiko ^{[7
]}

Seo, Yasushi ^{[7
]}

Azuma, Takeshi ^{[7
]}

Hotta, Hak ^{[1
]}

机构：

[1] Kobe Univ, Grad Sch Med, Ctr Infect Dis, Div Microbiol, Kobe, Hyogo 657, Japan

[2] Suez Canal Univ, Dept Virol, Fac Vet Med, Ismailia, Egypt

[3] Kobe Asahi Hosp, Div Gastroenterol, Kobe, Hyogo, Japan

[4] Hyogo Prefectural Kakogawa Med Ctr, Dept Gastroenterol, Kakogawa, Hyogo, Japan

[5] Nippon Steel Hirohata Hosp, Dept Internal Med, Himeji, Hyogo, Japan

[6] Konan Hosp, Dept Internal Med, Kobe, Hyogo, Japan

[7] Kobe Univ, Grad Sch Med, Dept Internal Med, Div Gastroenterol, Kobe, Hyogo 657, Japan

来源：

PLOS ONE | 2012年 / 7卷 / 02期

基金：

日本科学技术振兴机构;

关键词：

NONSTRUCTURAL PROTEIN 5A; SUSTAINED VIROLOGICAL RESPONSE; SENSITIVITY-DETERMINING REGION; ACID SUBSTITUTION PATTERN; VIRAL LOAD; COMBINATION THERAPY; PLUS RIBAVIRIN; MUTATIONS; 1B; ASSOCIATION;

D O I：

10.1371/journal.pone.0030513

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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.

引用

页数：10

共 39 条

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