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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 岡田, 誠治 Hattori, Shinichiro Ide, Kazuhiko Nakata, Hirotomo Harada, Hideki Suzu, Shinya Ashida, Noriyuki Kogo, Satoru Hayakawa, Hiroyuki ハヤカワ, ヒロユキ Hayakawa ハヤカワ Hiroyuki ヒロユキ Mitsuya, Hiroaki 岡田, 誠治 オカダ, セイジ Okada, Seiji 岡田 オカダ Okada 誠治 セイジ Seiji © 2009, American Society for Microbiology. All Rights Reserved. 493 HIV-1 mouse model nucleoside reverse transcriptase inhibitors NRTI 4’-ethynyl-2-fluoro-2’-deoxyadenosine EFdA application/pdf 論文(Article) 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. http://aac.asm.org/cgi/content/abstract/53/9/3887?ck=nck American Society for Microbiology 2009-09 eng journal article AM http://hdl.handle.net/2298/12909 https://kumadai.repo.nii.ac.jp/records/23011 19546363 10.1128/AAC.00270-09 00664804 AA00542574 Antimicrobial Agents and Chemotherapy 53 9 3887 3893 https://kumadai.repo.nii.ac.jp/record/23011/files/Hattori 77.pdf application/pdf 476.8 kB 2020-03-02