Details

Autor(en) / Beteiligte

• Lee, J., Sungkyunkwan University, Suwon, Republic of Korea
• Byeon, S.E., Sungkyunkwan University, Suwon, Republic of Korea
• Jung, J.Y., Sungkyunkwan University, Suwon, Republic of Korea
• Kang, M.H., Sungkyunkwan University, Suwon, Republic of Korea
• Park, Y.J., Sungkyunkwan University, Suwon, Republic of Korea
• Jung, K.E., 1ST PHARM 231, Siheung, Republic of Korea
• Bae, Y.S., Sungkyunkwan University, Suwon, Republic of Korea

Titel

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

Ist Teil von

• Molecules and Cells, 2015, 38(2), , pp.122-129

Ort / Verlag

United States: Korean Society for Molecular and Cellular Biology

Erscheinungsjahr

2015

Link zum Volltext

Quelle

SpringerLink

Beschreibungen/Notizen

• 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.