Molecules and Cells

Korean Society for Molecular and Cellular Biology (한국분자세포생물학회)
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Azasugar-Containing Phosphorothioate Oligonucleotide (AZPSON) DBM-2198 Inhibits Human Immunodeficiency Virus Type 1 (HIV-1) Replication by Blocking HIV-1 gp120 without Affecting the V3 Region

  • Lee, Jinjoo (Department of Biological Science, Sungkyunkwan University) ;
  • Byeon, Se Eun (Department of Biological Science, Sungkyunkwan University) ;
  • Jung, Ju Yeol (Department of Biological Science, Sungkyunkwan University) ;
  • Kang, Myeong-Ho (Department of Biological Science, Sungkyunkwan University) ;
  • Park, Yu-Jin (Department of Biological Science, Sungkyunkwan University) ;
  • Jung, Kyeong-Eun (ST PHARM) ;
  • Bae, Yong-Soo (Department of Biological Science, Sungkyunkwan University)
  • Received : 2014.05.15
  • Accepted : 2014.11.03
  • Published : 2015.02.28
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Abstract

DBM-2198, a six-membered azasugar nucleotide (6-AZN)-containing phosphorothioate (P = S) oligonucleotide (AZPSON), was described in our previous publication [Lee et al. (2005)] with regard to its antiviral activity against a broad spectrum of HIV-1 variants. This report describes the mechanisms underlying the anti-HIV-1 properties of DBM-2198. The LTR-mediated reporter assay indicated that the anti-HIV-1 activity of DBM-2198 is attributed to an extracellular mode of action rather than intracellular sequence-specific antisense activity. Nevertheless, the antiviral properties of DBM-2198 and other AZPSONs were highly restricted to HIV-1. Unlike other P = S oligonucleotides, DBM-2198 caused no host cell activation upon administration to cultures. HIV-1 that was pre-incubated with DBM-2198 did not show any infectivity towards host cells whereas host cells pre-incubated with DBM-2198 remained susceptible to HIV-1 infection, suggesting that DBM-2198 acts on the virus particle rather than cell surface molecules in the inhibition of HIV-1 infection. Competition assays for binding to HIV-1 envelope protein with anti-gp120 and anti-V3 antibodies revealed that DBM-2198 acts on the viral attachment site of HIV-1 gp120, but not on the V3 region. This report provides a better understanding of the antiviral mechanism of DBM-2198 and may contribute to the development of a potential therapeutic drug against a broad spectrum of HIV-1 variants.

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