D'Cruz Osmond J, Uckun Fatih M
Parker Hughes Institute, St Paul, MN 55113, USA.
Am J Reprod Immunol. 2007 May;57(5):353-60. doi: 10.1111/j.1600-0897.2007.00478.x.
SCID mice reconstituted with human peripheral blood lymphocytes (PBL) are amenable to vaginal transmission of HIV-1. We investigated the effectiveness of this model to establish systemic HIV-1 infection.
Eighty progesterone-primed C.B-17 SCID mice were reconstituted with human-PBLs and intravaginally inoculated with CCR5 HIV-1 (BaL or 92BR09) infected human-PBLs in the presence of human semen. After two weeks, viral RNA load in spleen, peritoneal lavage (PL), and serum was quantitated by the nucleic acid sequence-based amplification method.
In five independent experiments, spleen from 8/60 (13.3%), PL from 7/60 (11.6%), and serum from 16/56 (28.5%) mice were positive for BaL HIV-1 infection. Similarly, spleen from 4/20 (20%), PL from 1/20 (5%) and serum from 5/20 (25%) mice vaginally inoculated with 92BR09-infected human-PBLs were positive for HIV-1. A one-sided power analysis using normal approximation revealed that at 5% significance level, the overall response rate need to increase form 0.29 to 0.9 and 80% of the control groups needs to achieve a response rate between 6/10 and 9/10 to make the assay feasible.
The incidence of vaginal transmission of CCR5 HIV-1 in the human-PBL-SCID mouse was low and variable, which constitutes a major disadvantage for preclinical evaluation of vaginal microbicides.
用人外周血淋巴细胞（PBL）重建的严重联合免疫缺陷（SCID）小鼠易受HIV-1的阴道传播感染。我们研究了该模型建立全身性HIV-1感染的有效性。
80只经孕酮预处理的C.B-17 SCID小鼠用人PBL进行重建，并在人精液存在的情况下经阴道接种CCR5 HIV-1（BaL或92BR09）感染的人PBL。两周后，通过基于核酸序列的扩增方法对脾脏、腹腔灌洗（PL）液和血清中的病毒RNA载量进行定量分析。
在五项独立实验中，接种BaL HIV-1的小鼠中，8/60（13.3%）的脾脏、7/60（11.6%）的PL液和16/56（28.5%）的血清呈HIV-1感染阳性。同样，接种92BR09感染的人PBL的小鼠中，4/20（20%）的脾脏、1/20（5%）的PL液和5/20（25%）的血清呈HIV-1感染阳性。使用正态近似法进行的单侧效能分析显示，在5%的显著性水平下，总体反应率需从0.29提高到0.9，且80%的对照组反应率需在6/10至9/10之间，该检测才可行。
人PBL-SCID小鼠中CCR5 HIV-1阴道传播的发生率较低且存在差异，这构成了阴道杀微生物剂临床前评估的一个主要不利因素。
