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タイトル :Potent activity of a nucleoside reverse transcriptase inhibitor, 4′-ethynyl-2-fluoro-2′-deoxyadenosine, against human immunodeficiency virus type 1 infection in a model using human peripheral blood mononuclear cell-transplanted NOD/SCID Janus kinase 3 knockout mice
著者 :Hattori, Shinichiro
Ide, Kazuhiko
Nakata, Hirotomo
Harada, Hideki
Suzu, Shinya
Ashida, Noriyuki
Kogo, Satoru
Hayakawa, Hiroyuki
Mitsuya, Hiroaki
Okada, Seiji
刊行年月日 :2009-9
収録雑誌名 :Antimicrobial Agents and Chemotherapy
巻 :53
号 :9
開始ページ :3887
終了ページ :3893
要約(Abstract) :4'-Ethynyl-2-fluoro-2'-deoxyadenosine(EFdA), a recently discovered nucleoside reverse transcriptase inhibitor (NRTI), exhibits a wide spectrum of wild-type and multi-drug-resistant clinical HIV-1 isolates (EC50: 0.0001–0.001μM). In the present study, we used human peripheral blood mononuclear cell (hu-PBMC)-transplanted human immunodeficiency virus type 1 (HIV)-infected, NOD/SCID, janus kinase-3-knock-out (NOJ) mice for in vivo evaluation of the anti-HIV activity of EFdA. Administration of EFdA decreased the replication and cytopathic effects of HIV-1 without identifiable adverse effects. In PBS-treated mice, the CD4+/ CD8+ cell ratio in the spleen was low (median: 0.04, range 0.02–0.49), while that in mice receiving EFdA was increased (median: 0.65, range 0.57–1.43). EFdA treatment significantly suppressed the number of HIV-1 RNA (median: 9.0×102 copies/ml, range: 8.1×102-1.1×103; versus 9.9×104 copies/ml, range: 8.1×102–1.1×103; P < 0.001) and p24 level in plasma (2.5×103 range: 8.2×102–5.6×103 pg/ml, versus 2.8×102 range: 8.2×101–6.3×102 pg/ml; p<0.001) and p24+ cells in the spleen (1.90 %, range: 0.33–3.68, versus median: 0.11 %, range: 0.00–1.00, p=0.003) in comparison with PBS-treated mice. These data suggest that EFdA is a promising candidate for a new age of HIV-1 chemotherapy and should be further developed as a potential therapy for individuals with multidrug-resistant HIV-1 variants.
URL :http://aac.asm.org/cgi/content/abstract/53/9/3887?ck=nck
収録種別 :雑誌掲載論文
出版社(者) :American Society for Microbiology
権利(Rights) :© 2009, American Society for Microbiology. All Rights Reserved.
URI :http://hdl.handle.net/2298/12909
このアイテムの引用には次の識別子を使用してください: http://hdl.handle.net/2298/12909