Transcriptome profiling of Plasmodium vivax in Saimiri monkeys identifies potential ligands for invasion
Transcriptome profiling of Plasmodium vivax in Saimiri monkeys identifies potential ligands for invasion
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DOI：
10.1073/pnas.1818485116
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发表时间：
2019-04-02
影响因子：
11.1
通讯作者：
Miller, Louis H.
中科院分区：
文献类型：
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作者：
Gunalan, Karthigayan;Sa, Juliana M.;Miller, Louis H.
与亚洲和拉丁美洲的情况不同，间日疟原虫感染在撒哈拉以南非洲是罕见的，这是由于缺乏Duffy血型抗原（Duffy抗原），这是间日疟原虫裂殖子入侵配体Duffy结合蛋白1（DBP 1）的唯一已知红细胞受体。然而，间日疟原虫感染已在整个非洲的达菲阴性个体中记录，表明间日疟原虫可能使用DBP 1以外的配体通过其他受体侵入达菲阴性红细胞。为了鉴定潜在的间日疟原虫配体，我们比较了用间日疟原虫萨尔瓦多I（Sal I）感染的Saimiri和Aotus猴红细胞中的寄生虫基因表达。DBP 1结合Aotus但不结合Saimiri红细胞;因此，间日疟原虫Sal I必须独立于DBP 1侵入Saimiri红细胞。当侵袭配体表达时，比较Saimiri和Aotus红细胞中晚期感染的RNA测序（RNAseq）数据，我们鉴定了属于富含抗原和裂殖子表面蛋白3（MSP 3）家族的基因，这些基因在Saimiri感染中比Aotus感染中表达更丰富。这些基因可能编码负责达菲阴性非洲人的间日疟原虫感染的潜在配体。
Unlike the case in Asia and Latin America, Plasmodium vivax infections are rare in sub-Saharan Africa due to the absence of the Duffy blood group antigen (Duffy antigen), the only known erythrocyte receptor for the P. vivax merozoite invasion ligand, Duffy binding protein 1 (DBP1). However, P. vivax infections have been documented in Duffy-negative individuals throughout Africa, suggesting that P. vivax may use ligands other than DBP1 to invade Duffy-negative erythrocytes through other receptors. To identify potential P. vivax ligands, we compared parasite gene expression in Saimiri and Aotus monkey erythrocytes infected with P. vivax Salvador I (Sal I). DBP1 binds Aotus but does not bind to Saimiri erythrocytes; thus, P. vivax Sal I must invade Saimiri erythrocytes independent of DBP1. Comparing RNA sequencing (RNAseq) data for late-stage infections in Saimiri and Aotus erythrocytes when invasion ligands are expressed, we identified genes that belong to tryptophan-rich antigen and merozoite surface protein 3 (MSP3) families that were more abundantly expressed in Saimiri infections compared with Aotus infections. These genes may encode potential ligands responsible for P. vivax infections of Duffy-negative Africans.