Erythrocyte Invasion and Merozoite Ligand Gene Expression in Severe and Mild Plasmodium falciparum Malaria
Erythrocyte Invasion and Merozoite Ligand Gene Expression in Severe and Mild Plasmodium falciparum Malaria
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DOI：
10.1086/649902
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发表时间：
2010-02-01
影响因子：
6.4
通讯作者：
Conway, David J.
中科院分区：
文献类型：
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作者：
Gomez-Escobar, Natalia;Amambua-Ngwa, Alfred;Conway, David J.
红细胞入侵对于疟疾寄生虫的复制和毒力至关重要。恶性疟原虫寄生虫使用不同的替代红细胞受体，并且红细胞结合抗原（EBA）蛋白和网织红细胞结合蛋白同源物（Rh）的表达有所不同。对冈比亚离体培养的 163 个临床分离株确定了 8 个不带内部终止密码子的 eba 和 Rh 蛋白编码基因的寄生虫入侵表型和裂殖期转录表达谱。用神经氨酸酶、胰蛋白酶或胰凝乳蛋白酶处理后，侵入红细胞的能力存在广泛的多样性，并且与轻度疟疾分离株相比，严重疟疾分离株受到胰蛋白酶处理的限制较少（第015页）。 eba 和 Rh 基因的表达谱显示出不同的簇，表明协调的替代转录。 5 个主要簇中差异最大的是 Rh2b，几乎没有 eba175 或 eba140 基因的表达（这些基因在其他 4 个簇中占主导地位）。特定转录本与寄生虫血症（Rh5 正相关，eba140 负相关；两者 P < .001）和患者年龄（eba181 正相关，eba175 负相关；两者 P < .01）显着相关，但与侵袭表型或疟疾严重程度无关。严重和轻度疟疾分离株在不同的表达簇中也均匀地呈现。
Erythrocyte invasion is central to malaria parasite replication and virulence. Plasmodium falciparum parasites use different alternative erythrocyte receptors and vary in expression of erythrocyte-binding antigenic (EBA) proteins and reticulocyte-binding protein homologues (Rh). Parasite invasion phenotypes and schizont-stage transcript expression profiles of the 8 eba and Rh protein-coding genes without internal stop codons were determined for 163 clinical isolates cultured ex vivo in The Gambia. There was extensive diversity in ability to invade erythrocytes treated with neuraminidase, trypsin, or chymotrypsin, and severe malaria isolates were less restricted by trypsin treatment than were mild malaria isolates (Pp. 015). Expression profiles of the eba and Rh genes showed distinct clusters indicating coordinated alternative transcription. The most divergent of 5 major clusters was dominated by Rh2b, with virtually no expression of eba175 or eba140 genes (which were dominant in the other 4 clusters). Particular transcripts were significantly correlated with parasitemia (Rh5 was positively correlated and eba140 negatively correlated; P < .001 for both) and age of patients (eba181 was positively correlated and eba175 negatively correlated; P < .01 for both) but not with invasion phenotypes or severity of malaria. Severe and mild malaria isolates were also evenly represented across the different expression clusters.