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对巴基斯坦慢性丙型肝炎患者中流行的HCV-3a的NS5A进行体外转录分析及其对抗病毒治疗的不同反应。

In-Vitro Transcription analysis of NS5A from HCV-3a circulating in Pakistani patients with chronic hepatitis C and their differential response to antiviral therapy.

作者信息

Bhatti Shameem, Manzoor Sobia, Parvaiz Fahed, Ashraf Javed, Javed Farakh

机构信息

Shameem Bhatti, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Bio-Sciences, National University of Sciences and Technology (NUST), Islamabad 44000, Pakistan.

Sobia Manzoor, PhD, Department of Healthcare Biotechnology, Atta-ur-Rahman School of Applied Bio-Sciences, National University of Sciences and Technology (NUST), Islamabad 44000, Pakistan.

出版信息

Pak J Med Sci. 2017 Sep-Oct;33(5):1236-1241. doi: 10.12669/pjms.335.12973.

DOI:10.12669/pjms.335.12973
PMID:29142571
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5673740/
Abstract

OBJECTIVE

Mutations in HCV nonstructural protein 5A (NS5A) play a vital role in virus resistance. The aim of this study was to develop a correlation between NS5A mutations (genotype 3a) and virological response towards interferon alpha (IFN-α) plus ribavirin therapy.

METHODS

In this study, which was conducted from 09-02-2013 to 25-11-2015 in the rural area of Province Sindh - Pakistan, total patients' responses to peg-IFN therapy were investigated. Patients were given peg-IFN therapy for 24 to 48 weeks and categorized as sustained virologic responders (SVR) or non-responders (NR) to HCV infection. HCV NS5A region (2215-2335) of genotype 3a was identified in both responders and non-responders.

RESULTS

Twenty-four NR with 24 SVR isolates showed significant mutations within the nonstructural protein 5A region in HCV genotype 3a. The New Zealand (NZL1) (GenBank D17763) differences were observed by using gene. The ISDR mutations for nonstructural protein 5A in non-responders have been reported as a possible explanation of HCV interferon resistance.

CONCLUSION

Based on these results, it is suggested that decreased SVR is caused by the increased mutations in nonstructural protein 5A sequences. When the sequence outside the Protein kinases R binding domain (PKRBD) (2281-2335) was examined, significant differentiations were observed among the SVR and NR classes at few amino acid strains.

摘要

目的

丙型肝炎病毒非结构蛋白5A(NS5A)突变在病毒耐药性中起关键作用。本研究旨在建立NS5A突变(3a基因型)与干扰素α(IFN-α)联合利巴韦林治疗的病毒学应答之间的相关性。

方法

本研究于2013年2月9日至2015年11月25日在巴基斯坦信德省农村地区进行,调查了患者对聚乙二醇干扰素治疗的总体反应。患者接受聚乙二醇干扰素治疗24至48周,并被分类为丙型肝炎病毒感染的持续病毒学应答者(SVR)或无应答者(NR)。在应答者和无应答者中均鉴定出3a基因型的丙型肝炎病毒NS5A区域(2215 - 2335)。

结果

24例无应答者和24例持续病毒学应答者的分离株在丙型肝炎病毒3a基因型的非结构蛋白5A区域显示出显著突变。使用基因观察到与新西兰分离株(NZL1)(GenBank D17763)的差异。无应答者中非结构蛋白5A的ISDR突变已被报道为丙型肝炎病毒干扰素耐药的一种可能解释。

结论

基于这些结果,提示持续病毒学应答降低是由非结构蛋白5A序列中突变增加所致。当检查蛋白激酶R结合域(PKRBD)(2281 - 2335)以外的序列时,在少数氨基酸位点的持续病毒学应答者和无应答者类别之间观察到显著差异。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff1a/5673740/2cdb44ee267d/PJMS-33-1236-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff1a/5673740/8ad81b1fd013/PJMS-33-1236-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff1a/5673740/bade25c387b5/PJMS-33-1236-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff1a/5673740/2cdb44ee267d/PJMS-33-1236-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff1a/5673740/8ad81b1fd013/PJMS-33-1236-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff1a/5673740/bade25c387b5/PJMS-33-1236-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff1a/5673740/2cdb44ee267d/PJMS-33-1236-g003.jpg

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Virol J. 2011 May 25;8:258. doi: 10.1186/1743-422X-8-258.
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