@article{oai:u-ryukyu.repo.nii.ac.jp:02015586,
 author = {大隈, 和 and Okuma, kazu},
 issue = {1・2},
 journal = {琉球医学会誌 = Ryukyu Medical Journal},
 month = {},
 note = {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., 論文},
 pages = {1--9},
 title = {［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},
 volume = {27},
 year = {2008}
}