Infection of rhesus macaques by SIVmac239 virus inoculated rectally

Abstract

目的:制备SIVmac239 恒河猴(Macaca mulatta) 细胞适应株病毒，模拟HIV 性传播感染特点进行恒 河猴直肠黏膜感染研究，探索引起系统性感染的病毒阈值水平与机体病毒、免疫学之间相关性，为我国艾滋病黏膜 疫苗等生物制剂有效性评价提供新的模型构建思路。方法:参照HIV 性传播自然感染剂量范围，选用SIVmac239 连续升高的3 种剂量直肠黏膜途径感染两只恒河猴，采取多种方法进行病毒血症和免疫反应特点分析。结果:两 只恒河猴经2 × 101 TCID50 和2 × 102 TCID50 病毒滴度2 次攻击后45 d，经检测均未建立系统性感染，病毒特异性免 疫反应均为阴性;第3 次2 × 103 TCID50 病毒滴度攻击后，M296 猴表现出典型的系统性感染特点，并诱导特异性免 疫反应。结论:确认了HIV 性传播过程中的病毒剂量效应关系，为预防性生物制剂的猴体有效性评价提供了新的 思路。同时，发现SIVmac239 Gag 区特异性的T 细胞免疫反应在病毒控制过程中发挥了关键作用，对于新一代艾滋 病黏膜疫苗的抗原选择具有指导性意义。

Objective: SIVmac239 virus was used to infect rhesus monkeys by rectal inoculation to mimic sexually transmitted HIV infection. Methods: According to the dosage ranges of natural sexual HIV infection，two monkeys were rectally infected with three different serial doses of SIVmac239 virus. Meanwhile，the data of viremia and immune response were analyzed. Results: Both two monkeys were negative by RT-PCR and ELISA method detection after serial challenge with 2 × 101 TCID50 and 2 × 102 TCID50 doses of virus. However，one monkey (M296) infected with 2 × 103 TCID50 for the third time established systemic infection and induced high level of humoral and cellular immune responses. Conclusion: In this study the dose-effect relationship on sexual HIV transmission was confirmed. The SIVmac239 Gag specific cellular immune response has been suggested to play a key role in virus control，indicating the significance of antigen epitope selection for the new generation of mucosal AIDS vaccine.