猴免疫缺陷病毒（SIV）在艾滋病模型恒河猴组织中的分布和载量测定

目的研究当艾滋病恒河猴模型的血浆病毒载量处于低水平或阴性时,猴免疫缺陷病毒（simian immunodeficiency viruses,SIV）在宿主组织中的分布情况。方法SIVmac251感染恒河猴10只,定期检测其血浆载量,感染病毒平均高峰时间第14天时,活检取淋巴结。选取感染18个月后病毒载量最低水平和阴性的2只艾滋病猴（SAIDS）,经安死术后取淋巴结、脾、肝、肺、肾、脑等组织,用原位杂交和实时荧光定量PCR的方法检测病毒在组织中的分布和组织中的病毒载量。结果感染后14d,10只猴血浆病毒载量达到10^7copies/mL,淋巴结组织病毒载量为10^5-10^8copies/g,原位杂交方法在腹股沟淋巴结中检测到强阳性斑点。感染后第18个月的2只猴,血浆病毒载量下降并维持不高于10^2copies/mL水平或阴性,但组织分布不尽相同,在肠系膜淋巴结、肾上腺、海马回、空肠、脾脏等组织中检测到10^5-10^6copies/g的病毒载量,于一只猴的脑积液中检测到10^3copies/mL的病毒载量。用原位杂交的方法在肠系膜淋巴结和空肠中检测到强阳性斑点,其它组织中未检测到阳性斑点。结论实验证实SAIDS猴在血浆病毒载量低甚至阴性时,病毒在不同组织中仍有分布,有些组织中甚至出现高病毒载量,提示在制备SIV/SAIDS模型中,尤其在药物筛选和疫苗评价时,应考虑组织病毒载量指标的测定和药物、疫苗对组织病毒的治疗清除作用的评价。

Localization of SIV in the Rhesus Macaque Tissues

Objective To investigate the localization and viral load of SIV in the tissues in rhesus macaques with simian AIDS when their plasma viral load became the lowest level or nearly negative. Method 10 Rhesus macaques were inoculated with SIVmac251. Rhe viral load in plasma was measured at intervals of 3-5 days in the first month and the inguinal lymph nodes were collected at day 14 post-infection （p. i. ）. Two macaques whose viral load in plasma was kept at a very low level or undetectable at 18 months post-infection, were sacrificed and tissue samples were collected. The presence of SIV was determined and quantified by in suit hybridization and real-time quantitative PCR. Results The virus load got peaks at about 14 days （the highest 10^7copies/mL in plasma and 10^5 - 10^8copies/g in inguinal lymph nodes） and cells expressing SIV RNA were detected in inguinal lymph nodes. At 18 months p. i., a very low viral load was detected in the blood, but SIV was demonstrated to be positively distributed and even had a high level in the mesenteric lymph node, suprarenal gland, gyrus hippocampus, jejunum and spleen. Conclusion These results indicate that SIV may be distributed in some other tissues when the plasma viral load is nearly negative. These findings are very meaningful in SIV/SHIV/SAIDS macaques involved in drug screening and evaluation of vaccines for HIV/AIDS.