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Type: Journal article
Title: Nucleic acid polymers inhibit duck hepatitis B virus infection in vitro
Author: Noordeen, F.
Vaillant, A.
Jilbert, A.
Citation: Antimicrobial Agents and Chemotherapy, 2013; 57(11):5291-5298
Publisher: Amer Soc Microbiology
Issue Date: 2013
ISSN: 0066-4804
Statement of
Faseeha Noordeen, Andrew Vaillant, Allison R. Jilbert
Abstract: Nucleic acid polymers (NAPs) utilize the sequence-independent properties of phosphorothioate oligonucleotides (PS-ONs) to target protein interactions involved in viral replication. NAPs are broadly active against a diverse range of enveloped viruses that use type I entry mechanisms. The antiviral activity of NAPs against hepatitis B virus (HBV) infection was assessed in vitro in duck hepatitis B virus (DHBV)-infected primary duck hepatocytes (PDH). NAPs efficiently entered PDH in the absence of any transfection agent and displayed antiviral activity at concentrations of 0.01 to 10 μM, measured by their ability to prevent the intracellular accumulation of DHBV surface antigen, which was independent of their nucleotide sequence and was specifically dependent on phosphorothioation. Higher levels of antiviral activity were observed with NAPs 40 nucleotides in length or longer. The fully degenerate NAP (REP 2006) was active during DHBV infection or when added 12 h after infection. In contrast, an acidic-pH-sensitive NAP (REP 2031) that was broadly active against other viruses displayed antiviral activity when present during DHBV infection but no activity when added 12 h after infection, suggesting that NAPs exert their postentry effect in an acidic environment unique to DHBV infection. Both REP 2006 and REP 2031 displayed negligible cytotoxicity in PDH at concentrations of up to 10 μM, as assessed using an XTT [2,3-bis-(2-methoxy-4-nitro-5-sulfophenyl)-2H-tetrazolium-5-carboxanilide] cytotoxicity assay. The antiviral activity of NAPs against DHBV in vitro was strictly dependent on their amphipathic character, suggesting that NAPs interact with amphipathic target(s) that are important for DHBV entry and postentry mechanisms required for infection.
Keywords: Hepatocytes; Animals; Hepatitis B Virus, Duck; Hepatitis B Surface Antigens; Antiviral Agents; Virus Replication; Cell Survival; Structure-Activity Relationship; Hydrogen-Ion Concentration; Virus Internalization; Phosphorothioate Oligonucleotides; Hydrophobic and Hydrophilic Interactions; Primary Cell Culture
Rights: Copyright © 2013, American Society for Microbiology. All Rights Reserved.
RMID: 0020132486
DOI: 10.1128/AAC.01003-13
Appears in Collections:Molecular and Biomedical Science publications

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