Inhibition of hepatitis c virus infection by dna aptamer against NS2 protein

Yimin Gao, Xiaoyan Yu, Binbin Xue, Fei Zhou, Xiaohong Wang, Darong Yang, Nianli Liu, Li Xu, Xiaohong Fang, Haizhen Zhu

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

NS2 protein is essential for hepatitis C virus (HCV) replication. NS2 protein was expressed and purified. Aptamers against NS2 protein were raised and antiviral effects of the aptamers were examined. The molecular mechanism through which the aptamers exert their anti-HCV activity was investigated. The data showed that aptamer NS2-3 inhibited HCV RNA replication in replicon cell line and infectious HCV cell culture system. NS2-3 and another aptamer NS2-2 were demonstrated to inhibit infectious virus production without cytotoxicity in vitro. They did not affect hepatitis B virus replication. Interferon beta (IFNb) and interferon-stimulated genes (ISGs) were not induced by the aptamers in HCV-infected hepatocytes. Furthermore, our study showed that N-terminal region of NS2 protein is involved in the inhibition of HCV infection by NS2-2. I861T within NS2 is the major resistance mutation identified. Aptamer NS2-2 disrupts the interaction of NS2 with NS5A protein. The data suggest that NS2-2 aptamer against NS2 protein exerts its antiviral effects through binding to the N-terminal of NS2 and disrupting the interaction of NS2 with NS5A protein. NS2-specific aptamer is the first NS2 inhibitor and can be used to understand the mechanisms of virus replication and assembly. It may be served as attractive candidates for inclusion in the future HCV direct-acting antiviral combination therapies.

Original languageEnglish (US)
Article numbere90333
JournalPloS one
Volume9
Issue number2
DOIs
StatePublished - Feb 28 2014

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Hepatitis Viruses
Hepatitis C virus
hepatitis
Virus Diseases
Viruses
Hepacivirus
viruses
Virus Replication
infection
virus replication
Proteins
proteins
Antiviral Agents
Interferon-beta
Hepatovirus
interferon-beta
Virus Assembly
hepatitis A
replicon
Replicon

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Inhibition of hepatitis c virus infection by dna aptamer against NS2 protein. / Gao, Yimin; Yu, Xiaoyan; Xue, Binbin; Zhou, Fei; Wang, Xiaohong; Yang, Darong; Liu, Nianli; Xu, Li; Fang, Xiaohong; Zhu, Haizhen.

In: PloS one, Vol. 9, No. 2, e90333, 28.02.2014.

Research output: Contribution to journalArticle

Gao, Y, Yu, X, Xue, B, Zhou, F, Wang, X, Yang, D, Liu, N, Xu, L, Fang, X & Zhu, H 2014, 'Inhibition of hepatitis c virus infection by dna aptamer against NS2 protein', PloS one, vol. 9, no. 2, e90333. https://doi.org/10.1371/journal.pone.0090333
Gao, Yimin ; Yu, Xiaoyan ; Xue, Binbin ; Zhou, Fei ; Wang, Xiaohong ; Yang, Darong ; Liu, Nianli ; Xu, Li ; Fang, Xiaohong ; Zhu, Haizhen. / Inhibition of hepatitis c virus infection by dna aptamer against NS2 protein. In: PloS one. 2014 ; Vol. 9, No. 2.
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