Inhibition of hepatitis C virus production by aptamers against the core protein

Shali Shi, Xiaoyan Yu, Yimin Gao, Binbin Xue, Xinjiao Wu, Xiaohong Wang, Darong Yang, Haizhen Zhu

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Hepatitis C virus (HCV) core protein is essential for virus assembly. HCV core protein was expressed and purified. Aptamers against core protein were raised through the selective evolution of ligands by the exponential enrichment approach. Detection of HCV infection by core aptamers and the antiviral activities of aptamers were characterized. The mechanism of their anti-HCV activity was determined. The data showed that selected aptamers against core specifically recognize the recombinant core protein but also can detect serum samples from hepatitis C patients. Aptamers have no effect on HCV RNA replication in the infectious cell culture system. However, the aptamers inhibit the production of infectious virus particles. Beta interferon (IFN-β) and interferon- stimulated genes (ISGs) are not induced in virally infected hepatocytes by aptamers. Domains I and II of core protein are involved in the inhibition of infectious virus production by the aptamers. V31A within core is the major resistance mutation identified. Further study shows that the aptamers disrupt the localization of core with lipid droplets and NS5A and perturb the association of core protein with viral RNA. The data suggest that aptamers against HCV core protein inhibit infectious virus production by disrupting the localization of core with lipid droplets and NS5A and preventing the association of core protein with viral RNA. The aptamers for core protein may be used to understand the mechanisms of virus assembly. Core-specific aptamers may hold promise for development as early diagnostic reagents and potential therapeutic agents for chronic hepatitis C.

Original languageEnglish (US)
Pages (from-to)1990-1999
Number of pages10
JournalJournal of Virology
Volume88
Issue number4
DOIs
StatePublished - Feb 1 2014

Fingerprint

Hepatitis C virus
Hepacivirus
Virus Assembly
Viral RNA
Proteins
proteins
Viruses
Interferon-beta
Chronic Hepatitis C
Virus Diseases
Hepatitis C
Virus Replication
droplets
Recombinant Proteins
Virion
Interferons
Antiviral Agents
Hepatocytes
RNA
Cell Culture Techniques

All Science Journal Classification (ASJC) codes

  • Microbiology
  • Immunology
  • Insect Science
  • Virology

Cite this

Shi, S., Yu, X., Gao, Y., Xue, B., Wu, X., Wang, X., ... Zhu, H. (2014). Inhibition of hepatitis C virus production by aptamers against the core protein. Journal of Virology, 88(4), 1990-1999. https://doi.org/10.1128/JVI.03312-13

Inhibition of hepatitis C virus production by aptamers against the core protein. / Shi, Shali; Yu, Xiaoyan; Gao, Yimin; Xue, Binbin; Wu, Xinjiao; Wang, Xiaohong; Yang, Darong; Zhu, Haizhen.

In: Journal of Virology, Vol. 88, No. 4, 01.02.2014, p. 1990-1999.

Research output: Contribution to journalArticle

Shi, S, Yu, X, Gao, Y, Xue, B, Wu, X, Wang, X, Yang, D & Zhu, H 2014, 'Inhibition of hepatitis C virus production by aptamers against the core protein', Journal of Virology, vol. 88, no. 4, pp. 1990-1999. https://doi.org/10.1128/JVI.03312-13
Shi, Shali ; Yu, Xiaoyan ; Gao, Yimin ; Xue, Binbin ; Wu, Xinjiao ; Wang, Xiaohong ; Yang, Darong ; Zhu, Haizhen. / Inhibition of hepatitis C virus production by aptamers against the core protein. In: Journal of Virology. 2014 ; Vol. 88, No. 4. pp. 1990-1999.
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