Vaginal transmission of cell-associated HIV-1 in the mouse is blocked by a topical, membrane-modifying agent.
Vaginal transmission of cell-associated HIV-1 in the mouse is blocked by a topical, membrane-modifying agent.
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细胞相关的 HIV-1 在小鼠体内的阴道传播可被局部膜修饰剂阻断。
DOI：
10.1172/jci13236
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发表时间：
2002
期刊：
影响因子：
--
通讯作者：
Markham,RichardB
中科院分区：
文献类型：
--
作者：
Khanna,KristenV;Whaley,KevinJ;Zeitlin,Larry;Moench,ThomasR;Mehrazar,Karim;Cone,RichardA;Liao,Zhaohao;Hildreth,JamesEK;Hoen,TimothyE;Shultz,Leonard;Markham,RichardB
由于HIV-1病毒粒子和HIV感染细胞都存在于受感染个体的精液和宫颈粘液中，因此HIV-1预防策略必须考虑无细胞病毒和细胞相关病毒。靶向HIV-1病毒体的抗体已被证明可以防止猕猴中无细胞病毒的阴道传播，但由于细胞相关传播尚未在该模型系统中得到可靠证明，因此尚未测试预防此类传播的策略。我们采用了一种小鼠模型，其中SCID小鼠携带人外周血白细胞（HuPBL）。在这些小鼠中，通过HIV感染细胞的跨上皮迁移介导，发生细胞相关但非无细胞的HIV-1传播的阴道传播。β-环糊精（β-CD）是一种胆固醇螯合剂，可干扰细胞迁移和病毒从脂筏出芽，局部应用可阻断细胞相关HIV-1的传播。HIV-1阴道传播的HuPBL-SCID模型应被证明可用于研究细胞相关HIV-1经粘膜HIV-1传播，以及用于筛选预防HIV-1性传播的潜在有效性的试剂。
Because both HIV-1 virions and HIV-infected cells are present in the semen and cervical mucus of infected individuals, HIV-1 prevention strategies must consider both cell-free and cell-associated virus. Antibodies that target HIV-1 virions have been shown to prevent vaginal transmission of cell-free virus in macaques, but since cell-associated transmission has not been reliably demonstrated in this model system, no strategies to prevent such transmission have been tested. We have employed a mouse model in which SCID mice carry human peripheral blood leukocytes (HuPBLs). In these mice, vaginal transmission of cell-associated, but not cell-free, HIV-1 transmission occurs, mediated by transepithelial migration of HIV-infected cells. Topical application of β-cyclodextrin (β-CD), a cholesterol-sequestering agent that interferes with cell migration and budding of virus from lipid rafts, blocks transmission of cell-associated HIV-1. The HuPBL-SCID model of vaginal HIV-1 transmission should prove useful for investigating cell-associated HIV-1 transmucosal HIV-1 transmission, as well as for screening reagents for their potential efficacy in preventing sexual HIV-1 transmission.