HIV Protease Inhibitors Inhibit the Development of Preerythrocytic-Stage Plasmodium Parasites
HIV Protease Inhibitors Inhibit the Development of Preerythrocytic-Stage Plasmodium Parasites
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DOI：
10.1086/594369
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发表时间：
2009-01-01
影响因子：
6.4
通讯作者：
Sinnis, Photini
中科院分区：
文献类型：
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作者：
Hobbs, Charlotte V.;Voza, Tatiana;Sinnis, Photini
最近的研究表明，人类免疫缺陷病毒（HIV）蛋白酶抑制剂（PI）发挥抑制作用的红细胞阶段的人疟疾寄生虫恶性疟原虫在体外和红细胞阶段的啮齿类疟疾寄生虫夏氏疟原虫在体内。虽然目前还不清楚HIV PI如何抑制寄生虫，但在红细胞期对寄生虫发育的影响是有效的。尚未研究对红细胞前期的影响。使用啮齿动物寄生虫伯氏疟原虫，我们筛选了一组HIV PI体外对红细胞前期阶段的影响。我们的数据表明，艾滋病毒PI洛匹那韦和沙奎那韦影响红细胞前期阶段的寄生虫体外发育。然后，我们评估了艾滋病毒PI的影响，在体内使用啮齿动物寄生虫约氏疟原虫红细胞前期阶段。我们发现洛匹那韦/利托那韦对肝脏期寄生虫发育具有剂量依赖性作用。鉴于撒哈拉以南非洲是艾滋病毒/艾滋病流行病与疟疾交叉的地方，这些结果值得在临床环境中进行分析。
Recent studies have demonstrated that human immunodeficiency virus (HIV) protease inhibitors (PIs) exert inhibitory effects on erythrocytic stages of the human-malaria parasite Plasmodium falciparum in vitro and on erythrocytic stages of the rodent-malaria parasite Plasmodium chabaudi in vivo. Although it remains unclear how HIV PIs inhibit the parasite, the effect seen on parasite development in the erythrocytic stages is potent. The effect on preerythrocytic stages has not yet been investigated. Using the rodent parasite Plasmodium berghei, we screened a panel of HIV PIs in vitro for effects on the preerythrocytic stages. Our data indicated that the HIV PIs lopinavir and saquinavir affect preerythrocytic-stage parasite development in vitro. We then evaluated the effect of HIV PIs on preerythrocytic stages in vivo using the rodent parasite Plasmodium yoelii. We found that lopinavir/ritonavir had a dose-dependent effect on liver-stage parasite development. Given that sub-Saharan Africa is where the HIV/AIDS pandemic intersects with malaria, these results merit analysis in clinical settings.