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在泰缅边境,恶性疟原虫分离株 PfEMP1 的遗传多样性和分布模式。

Genetic diversity and distribution patterns of PfEMP1 in Plasmodium falciparum isolates along the Thai-Myanmar border.

机构信息

Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Khlong Luang, Pathum Thani 12120, Thailand.

Graduate Program in Bioclinical Sciences, Chulabhorn International College of Medicine, Thammasat University, Khlong Luang, Pathum Thani 12120, Thailand; Center of Excellence in Pharmacology and Molecular Biology of Malaria and Cholangiocarcinoma, Chulabhorn International College of Medicine, Thammasat University, Khlong Luang, Pathum Thani 12120, Thailand.

出版信息

Parasitol Int. 2021 Oct;84:102397. doi: 10.1016/j.parint.2021.102397. Epub 2021 May 24.

Abstract

Duffy binding-like domain (DBL) and cysteine-rich interdomain region (CIDR) domain genes of Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) encode malaria virulence proteins. The variants of these genes have been reported to be associated with severe/complicated malaria. The present study investigated the prevalence and distribution patterns of DBLα0.6/9, DBLα1.1, DBLα1 not var3 genes, DBLα2/α1.1/2/4/7, DBLβ12 & DBLβ3/5, DBLε8, CIDRα1.4, and CIDRα1.6 of P. falciparum isolates along the Thai-Myanmar border. The association between PfEMP1 variants and parasite density was also investigated. Two hundred and thirteen finger-prick dried blood spot (DBS) or whole blood samples were collected in 2007 and 2015, from patients with acute uncomplicated P. falciparum in Tak, Kanchanaburi, and Ranong provinces. Analysis of the variant genes was performed using polymerase chain reaction (PCR). The DBLs variant which was found at the highest and lowest frequencies in the three provinces were DBLα1 not var3 (72.77%), and DBLε8 (17.37%). The two CIDR domain variants were found at relatively lower frequencies compared with DBL domain variants (9.9% and 30.1%). P. falciparum isolates carrying the four PfEMP1 variants, i.e., DBLα0.6/9, DBLα1.1, DBLα2/α.1.1/2/4/7, and DBLε8 were found to be significantly associated with low parasitemia. Both DBLα0.6/9 and DBLα2/α1.1/2/4/7 variant genes which were present at high frequencies in this border area could be potential candidate markers for predicting P. falciparum hyperparasitemia and in this border area. Furthermore, the information could be exploited as candidate proteins for the development of an effective malaria vaccine in specific malaria-endemic areas.

摘要

疟原虫红细胞膜蛋白 1(PfEMP1)的 Duffy 结合样域(DBL)和富含半胱氨酸的域间区(CIDR)域基因编码疟疾毒力蛋白。这些基因的变异已被报道与严重/复杂疟疾有关。本研究调查了沿泰国-缅甸边境地区恶性疟原虫分离株中 DBLα0.6/9、DBLα1.1、DBLα1 非 var3 基因、DBLα2/α1.1/2/4/7、DBLβ12 和 DBLβ3/5、DBLε8、CIDRα1.4 和 CIDRα1.6 的流行率和分布模式。还研究了 PfEMP1 变异体与寄生虫密度之间的关系。2007 年和 2015 年在达府、北碧府和拉廊府采集了 213 份手指刺破干血斑(DBS)或全血样本,这些样本来自患有急性无并发症恶性疟原虫的患者。使用聚合酶链反应(PCR)分析变体基因。在这三个省中,发现 DBLα1 非 var3(72.77%)和 DBLε8(17.37%)的频率最高和最低。两个 CIDR 结构域变体的频率与 DBL 结构域变体相比相对较低(9.9%和 30.1%)。携带四种 PfEMP1 变体(即 DBLα0.6/9、DBLα1.1、DBLα2/α1.1/2/4/7 和 DBLε8)的恶性疟原虫分离株与低寄生虫血症显著相关。在这个边境地区,高频率存在的 DBLα0.6/9 和 DBLα2/α1.1/2/4/7 变体基因可能是预测恶性疟原虫高寄生虫血症的潜在候选标志物。此外,这些信息可被利用为在特定疟疾流行地区开发有效疟疾疫苗的候选蛋白。

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