Employing NOD/SCID/Jak3^−/− mice transplanted with human PBMCs (hNOJ mice) and replication-competent, red-fluorescent-protein (mCherry; mC)-labeled HIV-1_JR-FL (HIV_mC), we examined whether early antiretroviral treatment blocked the establishment of HIV-1 infection. The use of hNOJ mice and HIV_mC enabled us to visually locate infection foci and to examine the early dynamics of HIV_mC infection without using a large amount of antiretroviral unlike in non-human primate models. Although when raltegravir (RAL) administration was begun 1 day after intraperitoneal (ip) inoculation of HIV_mC, no plasma p24 or plasma HIV-1-RNA (pRNA) were detected in 10 of 12 hNOJ (hNOJ_mC^RAL+) mice as assessed on the last day of the 14-day continuous twice-daily RAL administration, all 10 untreated hNOJ_mC (hNOJ_mC^RAL−) mice became positive for p24 and pRNA and had significantly swollen lymph nodes in peritoneal cavity and abundant p24⁺/mC⁺/CD3⁺/CD4⁺ T cells and p24⁺/mC⁺/CD68⁺ monocytes/macrophages were identified in their omenta and mesenteric lymphoid tissues/lymph nodes upon necropsy of the mice on day 14. In 12 hNOJ_mC^RAL+ mice, no significantly swollen lymph nodes were seen compared to hNOJ_mC^RAL− mice; however, in the omentum of the 2 hNOJ_mC^RAL+ mice that were positive for pRNA and in site RNA, mC⁺/p24⁺/CD3⁺/CD83⁺ cells were identified, suggesting that viral breakthrough occurred later in the observation period. The present data suggest that the use of hNOJ mouse model and HIV_mC may shed light on the study of early-phase dynamics of HIV-1 infection and cellular events in post-exposure/pre-exposure prophylaxis.

使用移植了人 PBMC 的 NOD/SCID/Jak3 ^−/−小鼠（hNOJ 小鼠）和具有复制能力的红色荧光蛋白（mCherry; mC）标记的 HIV-1 _JR-FL (HIV _mC )，我们检查了是否早期抗逆转录病毒治疗阻止了 HIV-1 感染的形成。与非人类灵长类动物模型不同，hNOJ 小鼠和 HIV _mC的使用使我们能够直观地定位感染灶并检查 HIV _mC感染的早期动态，而无需使用大量抗逆转录病毒药物。尽管在腹膜内 ( ip ) 接种 HIV _mC 1 天后开始给予拉替拉韦 (RAL)，但根据评估，在 12 只 hNOJ (hNOJ _mC ^RAL+ ) 小鼠中，有 10 只未检测到血浆 p24 或血浆 HIV-1-RNA (pRNA)。在连续每日两次 RAL 给药 14 天的最后一天，所有 10 只未治疗的 hNOJ _mC (hNOJ _mC ^RAL− ) 小鼠均呈 p24 和 pRNA 阳性，腹膜腔淋巴结明显肿胀，p24 ⁺ /mC ⁺ / 丰富第 14 天尸检小鼠时，在其网膜和肠系膜淋巴组织/淋巴结中鉴定出 CD3 ⁺ /CD4 ⁺ T 细胞和 p24 ⁺ /mC ⁺ /CD68 ⁺单核细胞/巨噬细胞。 在 12 只 hNOJ _mC ^RAL+小鼠中，与 hNOJ _mC ^RAL−小鼠相比，没有观察到明显肿胀的淋巴结；然而，在 pRNA 和位点RNA 呈阳性的 2 只 hNOJ _mC ^RAL+小鼠的网膜中，发现了 mC ⁺ /p24 ⁺ /CD3 ⁺ /CD83 ⁺细胞，表明病毒突破发生在观察期后期。目前的数据表明，hNOJ 小鼠模型和 HIV _mC的使用可能有助于研究 HIV-1 感染的早期动态以及暴露后/暴露前预防中的细胞事件。