Inhibition of hepatitis C virus infection by NS5A-specific aptamer

Xiaoyan Yu, Yimin Gao, Binbin Xue, Xiaohong Wang, Darong Yang, Yuwen Qin, Rong Yu, Nianli Liu, Li Xu, Xiaohong Fang, Haizhen Zhu

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

To increase efficacy of hepatitis C treatment, future regiments will incorporate multiple direct-acting antiviral drugs. HCV NS5A protein was expressed and purified. Aptamers against NS5A were screened and obtained by the selective evolution of ligands by exponential enrichment approach and the antiviral actions of the aptamers were tested. The mechanisms through which the aptamers exert their antiviral activity were explored. The aptamers NS5A-4 and NS5A-5 inhibit HCV RNA replication and infectious virus production without causing cytotoxicity in human hepatocytes. The aptamers do not affect hepatitis B virus replication in HepG2.2.15 cells. Interferon beta (IFN-β) and interferon-stimulated genes (ISGs) are not induced by the aptamers in HCV-infected hepatocytes. Further study shows that domain I and domain III of NS5A protein are involved in the suppression of HCV RNA replication and infectious virus production by NS5A-4. Y2105H within NS5A is the major resistance mutation identified. NS5A aptamer disrupts the interaction of NS5A with core protein. The data suggest that the aptamers against NS5A protein may exert antiviral effects through inhibiting viral RNA replication, preventing the interaction of NS5A with core protein. Aptamers for NS5A may be used to understand the mechanisms of virus replication and assembly and served as potential therapeutic agents for hepatitis C.

Original languageEnglish (US)
Pages (from-to)116-124
Number of pages9
JournalAntiviral Research
Volume106
Issue number1
DOIs
StatePublished - Jan 1 2014

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Virus Diseases
Hepacivirus
Virus Replication
Antiviral Agents
Interferon-beta
Hepatitis C
Proteins
Hepatocytes
RNA
Virus Assembly
Viral RNA
Hepatitis B virus
Ligands
Mutation
Genes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Virology

Cite this

Inhibition of hepatitis C virus infection by NS5A-specific aptamer. / Yu, Xiaoyan; Gao, Yimin; Xue, Binbin; Wang, Xiaohong; Yang, Darong; Qin, Yuwen; Yu, Rong; Liu, Nianli; Xu, Li; Fang, Xiaohong; Zhu, Haizhen.

In: Antiviral Research, Vol. 106, No. 1, 01.01.2014, p. 116-124.

Research output: Contribution to journalArticle

Yu, X, Gao, Y, Xue, B, Wang, X, Yang, D, Qin, Y, Yu, R, Liu, N, Xu, L, Fang, X & Zhu, H 2014, 'Inhibition of hepatitis C virus infection by NS5A-specific aptamer', Antiviral Research, vol. 106, no. 1, pp. 116-124. https://doi.org/10.1016/j.antiviral.2014.03.020
Yu, Xiaoyan ; Gao, Yimin ; Xue, Binbin ; Wang, Xiaohong ; Yang, Darong ; Qin, Yuwen ; Yu, Rong ; Liu, Nianli ; Xu, Li ; Fang, Xiaohong ; Zhu, Haizhen. / Inhibition of hepatitis C virus infection by NS5A-specific aptamer. In: Antiviral Research. 2014 ; Vol. 106, No. 1. pp. 116-124.
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