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
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Screening for novel mutations associated with PMPA resistance in rhesus macaque-adapted SIVmac239 strain
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    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。

    Abstract:

    Objective To make sure the mutation sites of simian immunodeficiency virus (SIVmac239) resistance to 9-(2-methoxy propyl phosphate) adenine (PMPA), to guide the using of SIV/rhesus monkey model in the evaluation of HIV-1 drug. Method Rhesus macaque (RM) were infected with a RM-adapted SIVmac239 strain, were treat with PMPA. And plasma viral load and peripheral CD4 T cells was measured at different time points. Then the drug sensitivity of the virus strain was detected using CEMx174 cells. At last, we screened the mutation sites of rt gene from the virus strain by single genome amplification. Results PMPA treatment can’t effectively reduce the plasma viral load and peripheral CD4 T cells count had no significant chance. Drug sensitivity experiments confirmed that the virus strain is of insensitive to PMPA. Sequence alignment found that S205L and M502I of viral rt gene may affect PMPA sensitivity. Conclusions This study provided some information for the rational use of SIV/rhesus monkey model and clinical treatment of HIV-1.

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王卫.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[J].中国比较医学杂志,2013,23(10).

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  • 收稿日期:2013-08-21
  • 最后修改日期:2013-08-26
  • 录用日期:2013-10-14
  • 在线发布日期: 2013-12-16
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