基于BALB/c裸小鼠构建SIV感染动物模型

Establishment of an animal model of SIV infection based on BALB/c nude mice

目的构建可进行猴免疫缺陷病毒(SIV)复制的裸小鼠模型,为抗艾滋病病毒药物筛选的体内实验提供一种廉价、易于操作的艾滋病小动物模型。方法向BALB/c裸小鼠腹腔内接种已感染猴免疫缺陷病毒(SIVmac251)的TZM-b1细胞,构建SIV体内复制的裸小鼠动物模型,通过采集小鼠血浆,进行反转录实时荧光定量聚合酶链反应法(RT-PCR)检测血浆中SIVmac251病毒载量,并且通过HE染色法检测小鼠主要器官的组织学改变,通过高效联合抗反转录病毒疗法(HAART)对该模型进行药物干预,验证该模型的抗病毒药物评价效果。结果 1)BALB/c裸小鼠成功接种已感染SIVmac251的TZM-b1细胞。2)连续7周在BALB/c裸小鼠血浆里检测出SIVmac 251病毒载量。3)在小鼠主要器官出现了组织学改变。4)验证了HAART对小鼠体内SIVmac 251复制的抑制作用。结论构建了支持SIV复制的小动物模型,该模型能够支持SIVmac251的复制,并表现出组织学病理变化,为研究抗艾滋病药物体内抑制病毒复制提供了廉价、易于操作的小动物模型。

Objective To establish a SIV infected animal model for providing an inexpensive, easy-to-operate small animal model for in vivo experiments in anti-HIV drug screening. Methods BALB/c nude mice were intraperitoneally inoculated with TZM-b1 cells infected with SIVmac251. Plasma viral load was tested by reverse transcription real-time fluorescent quantitative PCR(RT-PCR). Pathological changes of major organs in mice were detected by HE staining. Mice were subjected to drug intervention with highly active anti-retroviral therapy(HAART) to evaluate the efficacy of the SIV-infected mouse model. Results 1. BALB/c nude mice were successfully inoculated with TZM-b1 cells infected with SIVmac251. 2. SIV load could be detected in the plasma of the BALB/c nude mice model for seven consecutive weeks. 3. There were marked histological changes in the main organs of the mice model. 4. The inhibition effect of HAART was verified on SIVmac251 virus replication in mice. Conclusion A small animal model of SIV infection is established, which can support the in vivo replication of the SIVmac251 and show pathological changes in main organs. This mouse model provides a cheap, easy-to-operate small animal model for studying anti-HIV drug effect in vivo.