Gunalan Karthigayan, Lo Eugenia, Hostetler Jessica B, Yewhalaw Delenasaw, Mu Jianbing, Neafsey Daniel E, Yan Guiyun, Miller Louis H
Laboratory of Malaria and Vector Research, National Institutes of Allergy and Infectious Diseases, National Institutes of Health, Rockville, MD 20852;
Program in Public Health, College of Health Sciences, University of California, Irvine, CA 92697;
Proc Natl Acad Sci U S A. 2016 May 31;113(22):6271-6. doi: 10.1073/pnas.1606113113. Epub 2016 May 17.
The ability of the malaria parasite Plasmodium vivax to invade erythrocytes is dependent on the expression of the Duffy blood group antigen on erythrocytes. Consequently, Africans who are null for the Duffy antigen are not susceptible to P. vivax infections. Recently, P. vivax infections in Duffy-null Africans have been documented, raising the possibility that P. vivax, a virulent pathogen in other parts of the world, may expand malarial disease in Africa. P. vivax binds the Duffy blood group antigen through its Duffy-binding protein 1 (DBP1). To determine if mutations in DBP1 resulted in the ability of P. vivax to bind Duffy-null erythrocytes, we analyzed P. vivax parasites obtained from two Duffy-null individuals living in Ethiopia where Duffy-null and -positive Africans live side-by-side. We determined that, although the DBP1s from these parasites contained unique sequences, they failed to bind Duffy-null erythrocytes, indicating that mutations in DBP1 did not account for the ability of P. vivax to infect Duffy-null Africans. However, an unusual DNA expansion of DBP1 (three and eight copies) in the two Duffy-null P. vivax infections suggests that an expansion of DBP1 may have been selected to allow low-affinity binding to another receptor on Duffy-null erythrocytes. Indeed, we show that Salvador (Sal) I P. vivax infects Squirrel monkeys independently of DBP1 binding to Squirrel monkey erythrocytes. We conclude that P. vivax Sal I and perhaps P. vivax in Duffy-null patients may have adapted to use new ligand-receptor pairs for invasion.
间日疟原虫侵入红细胞的能力取决于红细胞上达菲血型抗原的表达。因此，缺乏达菲抗原的非洲人不易感染间日疟原虫。最近，已记录到缺乏达菲抗原的非洲人感染间日疟原虫的情况，这增加了一种可能性，即间日疟原虫这种在世界其他地区的致病性病原体，可能会在非洲扩大疟疾疫情。间日疟原虫通过其达菲结合蛋白1（DBP1）与达菲血型抗原结合。为了确定DBP1中的突变是否导致间日疟原虫能够结合缺乏达菲抗原的红细胞，我们分析了从居住在埃塞俄比亚的两名缺乏达菲抗原的个体身上获得的间日疟原虫，在那里缺乏达菲抗原和具有达菲抗原的非洲人毗邻而居。我们确定，尽管这些寄生虫的DBP1含有独特序列，但它们无法结合缺乏达菲抗原的红细胞，这表明DBP1中的突变并不能解释间日疟原虫感染缺乏达菲抗原的非洲人的能力。然而，在这两例缺乏达菲抗原的间日疟原虫感染中，DBP1出现了异常的DNA扩增（三倍和八倍拷贝），这表明DBP1的扩增可能是为了使其能够与缺乏达菲抗原的红细胞上的另一种受体进行低亲和力结合。事实上，我们发现萨尔瓦多（Sal）I型间日疟原虫感染松鼠猴，与DBP1与松鼠猴红细胞的结合无关。我们得出结论，间日疟原虫Sal I型以及可能在缺乏达菲抗原的患者体内的间日疟原虫可能已经适应使用新的配体 - 受体对进行入侵。
