Altered Plasmodium falciparum Sensitivity to the Antiretroviral Protease Inhibitor Lopinavir Associated with Polymorphisms in pfmdr1.
Altered Plasmodium falciparum Sensitivity to the Antiretroviral Protease Inhibitor Lopinavir Associated with Polymorphisms in pfmdr1.
复制标题
恶性疟原虫对抗逆转录病毒蛋白酶抑制剂洛匹那韦的敏感性改变与 pfmdr1 多态性相关。
DOI：
10.1128/aac.01949-16
复制
发表时间：
2017
影响因子：
4.9
通讯作者：
Rosenthal,PhilipJ
中科院分区：
文献类型：
--
作者：
Sonoiki,Ebere;Nsanzabana,Christian;Legac,Jennifer;Sindhe,KirthanaMV;DeRisi,Joseph;Rosenthal,PhilipJ
艾滋病毒蛋白酶抑制剂洛匹那韦抑制恶性疟原虫天冬氨酸蛋白酶（plasmepsin）和寄生虫发育，接受洛匹那韦-利托那韦治疗的儿童比接受其他抗逆转录病毒治疗的儿童发生疟疾的次数更少。在体外试验中选择了对洛匹那韦耐药超过19个月，敏感性降低了14倍。耐药寄生虫的全基因组测序显示pfmdr 1基因突变和拷贝数增加，以及一种功能未知的蛋白质突变，但在纤溶酶基因中没有多态性。
The HIV protease inhibitor lopinavir inhibits Plasmodium falciparum aspartic proteases (plasmepsins) and parasite development, and children receiving lopinavir-ritonavir experienced fewer episodes of malaria than those receiving other antiretroviral regimens. Resistance to lopinavir was selectedin vitroover ∼9 months, with ∼4-fold decreased sensitivity. Whole-genome sequencing of resistant parasites showed a mutation and increased copy number inpfmdr1and a mutation in a protein of unknown function, but no polymorphisms in plasmepsin genes.