Inhibition of hepatitis C virus infection by DNA aptamer against envelope protein

Darong Yang, Xianghe Meng, Qinqin Yu, Li Xu, Ying Long, Bin Liu, Xiaohong Fang, Haizhen Zhu

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Hepatitis C virus (HCV) envelope protein (E1E2) is essential for virus binding to host cells. Aptamers have been demonstrated to have strong promising applications in drug development. In the current study, a cDNA fragment encoding the entire E1E2 gene of HCV was cloned. E1E2 protein was expressed and purified. Aptamers for E1E2 were selected by the method of selective evolution of ligands by exponential enrichment (SELEX), and the antiviral actions of the aptamers were examined. The mechanism of their antiviral activity was investigated. The data show that selected aptamers for E1E2 specifically recognize the recombinant E1E2 protein and E1E2 protein from HCV-infected cells. CD81 protein blocks the binding of aptamer E1E2-6 to E1E2 protein. Aptamers against E1E2 inhibit HCV infection in an infectious cell culture system although they have no effect on HCV replication in a replicon cell line. Beta interferon (IFN) and IFN-stimulated genes (ISGs) are not induced in virus-infected hepatocytes with aptamer treatment, suggesting that E1E2-specific aptamers do not induce innate immunity. E2 protein is essential for the inhibition of HCV infection by aptamer E1E2-6, and the aptamer binding sites are located in E2. Q412R within E1E2 is the major resistance substitution identified. The data indicate that an aptamer against E1E2 exerts its antiviral effects through inhibition of virus binding to host cells. Aptamers against E1E2 can be used with envelope protein to understand the mechanisms of HCV entry and fusion. The aptamers may hold promise for development as therapeutic drugs for hepatitis C patients.

Original languageEnglish (US)
Pages (from-to)4937-4944
Number of pages8
JournalAntimicrobial Agents and Chemotherapy
Volume57
Issue number10
DOIs
StatePublished - Oct 1 2013

Fingerprint

Nucleotide Aptamers
Virus Diseases
Hepacivirus
Proteins
Antiviral Agents
Virus Attachment
Viral Envelope Proteins
Virus Internalization
Replicon
Interferon-beta
Hepatitis C
Virus Replication
Protein C
Recombinant Proteins
Innate Immunity
Protein Binding
Pharmaceutical Preparations
Interferons
Genes
Hepatocytes

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

Inhibition of hepatitis C virus infection by DNA aptamer against envelope protein. / Yang, Darong; Meng, Xianghe; Yu, Qinqin; Xu, Li; Long, Ying; Liu, Bin; Fang, Xiaohong; Zhu, Haizhen.

In: Antimicrobial Agents and Chemotherapy, Vol. 57, No. 10, 01.10.2013, p. 4937-4944.

Research output: Contribution to journalArticle

Yang, Darong ; Meng, Xianghe ; Yu, Qinqin ; Xu, Li ; Long, Ying ; Liu, Bin ; Fang, Xiaohong ; Zhu, Haizhen. / Inhibition of hepatitis C virus infection by DNA aptamer against envelope protein. In: Antimicrobial Agents and Chemotherapy. 2013 ; Vol. 57, No. 10. pp. 4937-4944.
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