猴免疫缺陷病毒(SIVmac239)恒河猴适应株耐9-(2-磷酸甲氧丙基)腺嘌呤(PMPA)突变位点筛查  

Screening of mutation sites associated with PMPA resistance in rhesus macaque-adapted SIVmac239 strain

作　　者：王卫[1] 鞠斌[1] 丛喆[1] 董志会 陈霆[1] 杜文达[1] 蒋虹[1] 魏强[1] 

机构地区：[1]北京协和医学院比较医学中心,中国医学科学院医学实验动物研究所,卫生部人类疾病比较医学重点实验室,国家中医药管理局人类疾病动物模型三级实验室,北京100021

出　　处：《中国比较医学杂志》2013年第10期44-48,57,共6页Chinese Journal of Comparative Medicine

基　　金：国家科技重大专项课题(2012ZX10004501-001)

摘　　要：目的初步明确猴免疫缺陷病毒(SIVmac239)耐9-(2-磷酸甲氧丙基)腺嘌呤(PMPA)突变基因位点,指导SIV/恒河猴模型在药物评价中的应用。方法 SIVmac239恒河猴适应株感染恒河猴,之后进行PMPA治疗,测定不同时间点血浆病毒载量和外周血CD4+T细胞数;使用CEMx174细胞进行药物敏感实验。单拷贝PCR测定病毒rt基因变异情况。结果 PMPA治疗不能有效降低感染猴血浆病毒载量,且对血CD4+T细胞数没有显著影响;细胞水平药物敏感实验证实该病毒株对PMPA不敏感。序列比对发现S205L和M502I可能影响到病毒对PMPA的药物敏感性。结论本研究为SIV/恒河猴模型的合理使用及HIV-1的临床治疗提供了信息。Objective To identify the mutation sites of simian immunodeficiency virus （ SIVmac239 ） resistant to 9-[ 2-（Phosphonomethoxy） propyl ] adenine （PMPA） , and to guide the application of SIV/rhesus monkey models in HIV-1 drug evaluation. Methods Rhesus monkeys （RM） infected with a RM-adapted SIVmac239 strain were treated with PMPA, and the plasma viral load and peripheral CD4^ ＋ T ceils were measured at different time points. Then the drug sensitivity of the virus strain was detected using CEMx174 cells. Finally, the mutation sites of rt gene from the virus strain were screened by single genome amplification. Results PMPA treatment did not effectively reduce the plasma viral load and did not significantly change the peripheral CD4^ ＋ T cell count. Drug sensitivity test confirmed that the virus strain is insensitive to PMPA. The results of sequence alignment indicated that S205L and M502I of viral rt gene may affect PMPA sensitivity. Conclusions The results of this study provide some information for the rational use of SIV/rhesus monkey models and clinical treatment of HIV-1 infection.

关 键 词：SIVMAC239 PMPA rt基因 耐药位点 

分 类 号：R33[医药卫生—人体生理学]