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伊朗分离株恶性疟原虫 knob 相关富含组氨酸蛋白(KAHRP)C 末端结构域(区域 III)的遗传多态性。

Genetic polymorphism at the C-terminal domain (region III) of knob-associated histidine-rich protein (KAHRP) of Plasmodium falciparum in isolates from Iran.

机构信息

Department of Medical Parasitology and Mycology, School of Public Health and Institute of Public Health Research, Tehran University of Medical Sciences (TUMS), P.O. Box 14155-6446, Tehran, Iran.

出版信息

Parasitol Res. 2011 Dec;109(6):1647-52. doi: 10.1007/s00436-011-2437-x. Epub 2011 May 20.

DOI:10.1007/s00436-011-2437-x
PMID:21594767
Abstract

The knob-associated histidine-rich protein (KAHRP) plays a major role in the virulence of Plasmodium falciparum and is one of the targets for molecular therapy. The primary structure of KAHRP of P. falciparum consists of three domains (regions I-III), of which the C-terminal domain (region III) is the most polymorphic segment of this protein. One of the main obstacles is genetic diversity in designing and developing of malaria control strategies such as molecular therapy and vaccines. The primary objective of the present study was to investigate and analyze the extent of genetic polymorphism at the region III of KAHRP of P. falciparum in isolates from Iran. A fragment of the kahrp gene spanning the C-terminal domain was amplified by nested PCR from 50 P. falciparum isolates collected from two malaria endemic areas of Iran during 2009 to August 2010 and sequenced. In this study, three allelic types were observed at the C-terminal domain of KAHRP on the basis of the molecular weight of nested PCR products and the obtained sequencing data. The presence of multiple alleles of the kahrp gene indicates that several P. falciparum strains exist in the malaria endemic areas of Iran. Our findings will be valuable in the design and the development of the molecular therapeutic reagents for falciparum malaria.

摘要

knob 相关组氨酸丰富蛋白(KAHRP)在恶性疟原虫的毒力中起着重要作用,是分子治疗的靶点之一。恶性疟原虫的 KAHRP 一级结构由三个结构域(区域 I-III)组成,其中 C 末端结构域(区域 III)是该蛋白最具多态性的片段。在设计和开发疟疾控制策略(如分子治疗和疫苗)方面,遗传多样性是主要障碍之一。本研究的主要目的是调查和分析 2009 年至 2010 年 8 月期间从伊朗两个疟疾流行地区采集的 50 株恶性疟原虫分离株中 KAHRP 区域 III 的遗传多态性程度。从 50 株恶性疟原虫分离株中扩增了嵌套 PCR 跨越 C 末端结构域的 kahrp 基因片段,并进行了测序。在这项研究中,根据嵌套 PCR 产物的分子量和获得的测序数据,在 KAHRP 的 C 末端结构域观察到三种等位基因类型。kahrp 基因的多个等位基因的存在表明,在伊朗的疟疾流行地区存在几种恶性疟原虫株。我们的研究结果将有助于设计和开发针对恶性疟原虫疟疾的分子治疗试剂。

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