CXCR4嗜性SHIVKU-1病毒静脉感染中国恒河猴初步研究

Characterization of a Chinese-origin rhesus macaque model of X4-tropic pathogenic SHIVKU-1 infection by intravenous injection

目的了解SHIVKU-1静脉途径感染中国恒河猴的感染特点及进展规律。方法两只健康中国恒河猴,静脉感染SHIVKU-1病毒,定期采样检测血浆病毒载量、CD4+/CD8+比值、CD4+T细胞绝对数变化和血清中抗SHIVKU-1特异性IgG抗体水平。多色流式技术分析外周血、腹股沟淋巴结和十二指肠粘膜固有层CD4+T淋巴细胞记忆细胞亚群变化。结果两只实验猴成功感染SHIVKU-1病毒,一直到感染后3个月均保持稳定水平的病毒载量。外周血CD4+T淋巴细胞下降明显,CD4+/CD8+T细胞比值严重倒置。CD4+Tcm细胞比例在经历了感染早期的下降后,大幅升高,尤其是外周血和淋巴结。CD4+Tem则在粘膜固有层中增加明显。结论 SHIVKU-1静脉途径成功感染了中国恒河猴,为SHIV/中国恒河猴疾病及评价模型的建立奠定了良好的基础,为今后使用此模型评价抗病毒药物或疫苗提供了条件。

Objective To study the characteristics of SHIVKU-1 infection in Chinese rhesus macaques and provide an animal platform in evaluation of the effectiveness of anti-HIV-1 drugs or vaccines with SHIVKU-1/rhesus animal model. Methods Two healthy Chinese-origin rhesus macaques, serum negative to SIV, SRV and STLV-1, were infected with SHIVKU-1 intravenously. CD4＋ and CD8 ＋ T cell subsets including memory CD4 ＋ T cell subset in the peripheral blood （PBL）, inguinal lymph nodes （ILN）, and intestinal lamina propria （LP） were analyzed by flow cytometry. Viral load was detected by real time RT-PCR, so was the specific IgG antibody titer against SHIVKU-1 in the plasma using ELISA. Results Both of the two rhesus macaques established systemic infection, keeping steady viral load in 3 months after infection. The monkey G1302V died 457 days post-infection. Peripheral CD4 ＋ T lymphocytes decreased significantlypost-infection, while the CD4＋/CD8 ＋ ratio went upside down. The proportion of CD4＋ Tcm cells experienced a decline in the early stage of infection and rose sharply, especially in the peripheral blood and lymph nodes. CD4 ＋ Tern increased significantly in the intestinal lamina propria. Conclusions A Chinese rhesus macaque model of SHIVKU-1 infection is successfully established by intravenous injection. It provides a choice to evaluate the efficiency of candidate vaccines or drugs aiming at the X4 tropic HIV, and for the pathogenesis studies as well.