title: 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.
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 oligonucleo-tides, 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.
authors.affiliation: Department of Biological Science, Sungkyunkwan University, Suwon 446-740, Korea.
authors.forename: Jinjoo
authors.initials: J
authors.lastname: Lee
authors.affiliation: Department of Biological Science, Sungkyunkwan University, Suwon 446-740, Korea.
authors.forename: Se Eun
authors.initials: SE
authors.lastname: Byeon
authors.affiliation: Department of Biological Science, Sungkyunkwan University, Suwon 446-740, Korea.
authors.forename: Ju Yeol
authors.initials: JY
authors.lastname: Jung
authors.affiliation: Department of Biological Science, Sungkyunkwan University, Suwon 446-740, Korea.
authors.forename: Myeong-Ho
authors.initials: MH
authors.lastname: Kang
authors.affiliation: Department of Biological Science, Sungkyunkwan University, Suwon 446-740, Korea.
authors.forename: Yu-Jin
authors.initials: YJ
authors.lastname: Park
authors.affiliation: Department of Biological Science, Sungkyunkwan University, Suwon 446-740, Korea.
authors.forename: Kyeong-Eun
authors.initials: KE
authors.lastname: Jung
authors.affiliation: Department of Biological Science, Sungkyunkwan University, Suwon 446-740, Korea.
authors.forename: Yong-Soo
authors.initials: YS
authors.lastname: Bae
mesh_terms: D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D019556:COS Cells; D002460:Cell Line; D002522:Chlorocebus aethiops; D015967:Gene Expression Regulation, Viral; D015699:HIV Envelope Protein gp120 / Q000378:metabolism*; D015497:HIV-1 / Q000187:drug effects*; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology*; D054735:Phosphorothioate Oligonucleotides / Q000494:pharmacology*; D010880:Piperidines / Q000494:pharmacology*; D053585:Virus Attachment / Q000187:drug effects; D014779:Virus Replication / Q000187:drug effects*
chemical_list: D019380:Anti-HIV Agents; C000602660:DBM 2198; D015699:HIV Envelope Protein gp120; D009838:Oligodeoxyribonucleotides; D054735:Phosphorothioate Oligonucleotides; D010880:Piperidines; C514793:gp120 protein, Human immunodeficiency virus 1
keywords: DBM-2198; V3; anti-HIV-1 mechanism; gp120; six-membered azasugar nucleotide (6-AZN)-containing phosphorothioate (P = S) oligonucleotide (AZPSON)