Okuma Kazu, Tanaka Reiko, Ogura Tomoyuki, Ito Mamoru, Kumakura Sei, Yanaka Mikiro, Nishizawa Masako, Sugiura Wataru, Yamamoto Naoki, Tanaka Yuetsu
Department of Immunology, Graduate School and Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
J Infect Dis. 2008 Jan 1;197(1):134-41. doi: 10.1086/524303.
CXCR4-tropic (X4) human immunodeficiency virus type 1 (HIV-1) does not efficiently infect and replicate in severe combined immunodeficiency (SCID) mice reconstituted with human peripheral blood mononuclear cells, termed "hu-PBL-SCID mice," due to, at least in part, relatively low levels of expression of the CXCR4 coreceptor. To overcome this limitation, interleukin (IL)-4-transgenic hu-PBL-SCID mice were derived that spontaneously synthesized human IL-4, which has been shown to enhance CXCR4 expression and promote X4 virus infection in vitro. Experiments reported here show that (1) synthesis of human IL-4 in vivo augmented CXCR4 expression on human CD4(+) lymphocytes and importantly led to productive infection of not only X4 HIV-1(NL4-3) but also multidrug-resistant primary clinical isolates and that (2) the in vivo infection could be significantly blocked by the administration of a CXCR4 antagonist. Altogether, IL-4-transgenic hu-PBL-SCID mice provide a useful model for X4 HIV-1 study and testing/screening of anti-X4 viral drugs.
趋化因子受体4型（CXCR4）嗜性的1型人类免疫缺陷病毒（HIV-1，简称X4型HIV-1），无法在用人外周血单个核细胞重建的严重联合免疫缺陷（SCID）小鼠（即“人外周血淋巴细胞-严重联合免疫缺陷小鼠”，简称“hu-PBL-SCID小鼠”）中有效地感染和复制，至少部分原因是CXCR4共受体的表达水平相对较低。为克服这一限制，构建了白细胞介素（IL）-4转基因hu-PBL-SCID小鼠，其可自发合成人IL-4，体外实验表明，人IL-4可增强CXCR4表达并促进X4病毒感染。本文报道的实验表明：（1）体内合成的人IL-4可增加人CD4(+)淋巴细胞上CXCR4的表达，重要的是，这不仅导致X4型HIV-1（NL4-3）产生有效感染，还能感染多药耐药的原发性临床分离株；（2）给予CXCR4拮抗剂可显著阻断体内感染。总之，IL-4转基因hu-PBL-SCID小鼠为X4型HIV-1研究以及抗X4病毒药物的测试/筛选提供了一个有用的模型。
