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[総説]HIV-1感染に対する新規治療法及び感染実験小動物モデルの開発
http://hdl.handle.net/20.500.12000/0002015586
http://hdl.handle.net/20.500.12000/00020155865dcf0823-4f2b-4369-ba63-9f10de8e2448
名前 / ファイル | ライセンス | アクション |
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Item type | デフォルトアイテムタイプ(フル)(1) | |||||||||
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公開日 | 2010-02-23 | |||||||||
タイトル | ||||||||||
タイトル | [総説]HIV-1感染に対する新規治療法及び感染実験小動物モデルの開発 | |||||||||
言語 | ja | |||||||||
タイトル | ||||||||||
タイトル | Development of a Novel Anti-HIV 1 Therapy and a Small Animal Model for the Testing of Anti-HIV 1 Drugs | |||||||||
言語 | en | |||||||||
作成者 |
大隈, 和
× 大隈, 和
× Okuma, kazu
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アクセス権 | ||||||||||
アクセス権 | open access | |||||||||
アクセス権URI | http://purl.org/coar/access_right/c_abf2 | |||||||||
権利情報 | ||||||||||
言語 | ja | |||||||||
権利情報 | 琉球医学会 | |||||||||
主題 | ||||||||||
言語 | en | |||||||||
主題Scheme | Other | |||||||||
主題 | HIV-1 | |||||||||
主題 | ||||||||||
言語 | en | |||||||||
主題Scheme | Other | |||||||||
主題 | VSV | |||||||||
主題 | ||||||||||
言語 | en | |||||||||
主題Scheme | Other | |||||||||
主題 | viral receptor | |||||||||
主題 | ||||||||||
言語 | en | |||||||||
主題Scheme | Other | |||||||||
主題 | animal model | |||||||||
主題 | ||||||||||
言語 | en | |||||||||
主題Scheme | Other | |||||||||
主題 | interleukin-4 | |||||||||
内容記述 | ||||||||||
内容記述タイプ | Other | |||||||||
内容記述 | Highly active anti-retroviral therapy (HAART) is effective against human immunodeficiency virus type 1 ( HIV-1) infection, but several severe problems such as occurrence of multi-drug resistant (MDR) viruses are emerging after use of the currently available drugs. Thus, development of novel therapeutics with a different mechanism of action is urgently needed. A recombinant vesicular stomatitis virus (VSV) lacking its G gene ($ \Delta $G) and instead encoding human CD4 and CXCR4 is known to control CXCR4-tropic (X4) HIV-1 infection in culture. To test the value of such a recombiant virus more, we constructed VSV $ \Delta $ Gs expressing CD4 and CCR5 with or without modified dendritic cellspecific ICAM-3 grabbing nonintegrin (DC-SIGN) from rhesus macaques and examined if these viruses were effective against simian immunodeficiency virus (SIV) infection in culture. Our data demonstrated that the VSV $ \Delta $ Gs specifically infected and killed SIVinfected cells, resulting in long-term control of SIV infection in vitro. These results indicate that such VSVs have potential for novel anti-HIV-1 therapeutic candidates. In addition, to determine therapeutic value of anti-HIV-1 drug candidates, it is crucial to test them in animal models before clinical trials. Severe combined immunodeficiency (SCID) mice reconstituted with human peripheral blood mononuclear cells (PBMCs),termed hu-PBLSCID mice or humanized mice, have served as such a valuable small animal model. However, there was a limitation on use of this model because X4 HIV-1 does not efficiently infect these mice due to, at least in part, relatively low levels of expression of the CXCR4 coreceptor. To solve this problem, we generated human interleukin (IL)-4-transgenic huPBL-SCID mice that spontaneously synthesized human IL-4 which has been shown to enhance CXCR4 expression and promote X4 HIV-1 infection in vitro and investigated if X4 virus efficiently infected these mice. Our study showed that in vivo synthesis of human IL-4 augmented CXCR4 expression on human CD4+ T cells and led to productive X4 HIV-1 infection, and that the in vivo infection was definitely blocked by CXCR4 antagonist administration. These data indicate that human IL-4-transgenic hu-PBL-SCID mice can be a useful model for the X4 HIV-1 study and the testing of anti-X4 HIV-1 drug candidates. | |||||||||
内容記述 | ||||||||||
内容記述タイプ | Other | |||||||||
内容記述 | 論文 | |||||||||
出版者 | ||||||||||
言語 | ja | |||||||||
出版者 | 琉球医学会 | |||||||||
出版者 | ||||||||||
言語 | en | |||||||||
出版者 | Ryukyu Medical Association | |||||||||
言語 | ||||||||||
言語 | jpn | |||||||||
資源タイプ | ||||||||||
資源タイプ | journal article | |||||||||
資源タイプ識別子 | http://purl.org/coar/resource_type/c_6501 | |||||||||
出版タイプ | ||||||||||
出版タイプ | VoR | |||||||||
出版タイプResource | http://purl.org/coar/version/c_970fb48d4fbd8a85 | |||||||||
収録物識別子 | ||||||||||
収録物識別子タイプ | ISSN | |||||||||
収録物識別子 | 1346-888X | |||||||||
収録物識別子 | ||||||||||
収録物識別子タイプ | ISSN | |||||||||
収録物識別子 | 0289-1530 | |||||||||
収録物識別子 | ||||||||||
収録物識別子タイプ | NCID | |||||||||
収録物識別子 | AN10369445 | |||||||||
収録物名 | ||||||||||
言語 | ja | |||||||||
収録物名 | 琉球医学会誌 = Ryukyu Medical Journal | |||||||||
書誌情報 |
巻 27, 号 1・2, p. 1-9, 発行日 2008 |