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Raltegravir blocks the infectivity of red-fluorescent-protein (mCherry)-labeled HIV-1JR-FL in the setting of post-exposure prophylaxis in NOD/SCID/Jak3−/− mice transplanted with human PBMCs
Antiviral Research ( IF 7.6 ) Pub Date : 2017-09-08 , DOI: 10.1016/j.antiviral.2017.09.003
Hiromi Ogata-Aoki , Nobuyo Higashi-Kuwata , Shin-ichiro Hattori , Hironori Hayashi , Matthew Danish , Manabu Aoki , Chiemi Shiotsu , Yumi Hashiguchi , Akinobu Hamada , Hisataka Kobayashi , Hironobu Ihn , Seiji Okada , Hiroaki Mitsuya

Employing NOD/SCID/Jak3−/− mice transplanted with human PBMCs (hNOJ mice) and replication-competent, red-fluorescent-protein (mCherry; mC)-labeled HIV-1JR-FL (HIVmC), we examined whether early antiretroviral treatment blocked the establishment of HIV-1 infection. The use of hNOJ mice and HIVmC enabled us to visually locate infection foci and to examine the early dynamics of HIVmC 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 HIVmC, no plasma p24 or plasma HIV-1-RNA (pRNA) were detected in 10 of 12 hNOJ (hNOJmCRAL+) mice as assessed on the last day of the 14-day continuous twice-daily RAL administration, all 10 untreated hNOJmC (hNOJmCRAL−) 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 hNOJmCRAL+ mice, no significantly swollen lymph nodes were seen compared to hNOJmCRAL− mice; however, in the omentum of the 2 hNOJmCRAL+ 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 HIVmC may shed light on the study of early-phase dynamics of HIV-1 infection and cellular events in post-exposure/pre-exposure prophylaxis.



中文翻译:

Raltegravir可以在人PBMC移植的NOD / SCID / Jak3 -/-小鼠暴露后预防的环境中,阻止红色荧光蛋白(mCherry)标记的HIV-1 JR-FL的感染性

使用移植了人P​​BMC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感染的建立。与非人类灵长类动物模型不同,使用hNOJ小鼠和HIV mC使我们能够直观地确定感染灶并检查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后1天开始raltegravir(RAL)给药,但在12 hNOJ(hNOJ)中的10个中未检测到血浆p24或血浆HIV-1-RNA(pRNA)在连续14天每天两次RAL给药的最后一天评估的mC RAL +)小鼠中,所有10只未经治疗的hNOJ mC(hNOJ mC RAL−)小鼠均对p24和pRNA呈阳性,并且腹膜腔和淋巴结中淋巴结明显肿大小鼠尸检第14天时,在其全向和肠系膜淋巴组织/淋巴结中鉴定到大量的p24 + / mC + / CD3 + / CD4 + T细胞和p24 + / mC + / CD68 +单核细胞/巨噬细胞。在12 hNOJ mC RAL +小鼠,与hNOJ mC相比,没有观察到明显的淋巴结肿大RAL-小鼠;然而,在两只对pRNA呈阳性的hNOJ mC RAL +小鼠的网膜中和在位RNA中,鉴定出了mC + / p24 + / CD3 + / CD83 +细胞,这表明在观察期的后期出现了病毒突破。目前的数据表明,hNOJ小鼠模型和HIV mC的使用可能为暴露后/暴露前预防中HIV-1感染的早期动态和细胞事件的研究提供启示。

更新日期:2017-09-08
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