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可变基因、恶性疟原虫红细胞表面蛋白1和人类宿主。

var genes, PfEMP1 and the human host.

作者信息

Flick Kirsten, Chen Qijun

机构信息

Microbiology and Tumour Biology Centre (MTC), Karolinska Institutet and Swedish Institute for Infectious Disease Control, Box 280, SE-171 77 Stockholm, Sweden.

出版信息

Mol Biochem Parasitol. 2004 Mar;134(1):3-9. doi: 10.1016/j.molbiopara.2003.09.010.

DOI:10.1016/j.molbiopara.2003.09.010
PMID:14747137
Abstract

Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) is an important virulence factor encoded by a family of roughly 60 var genes and is used by the parasite to interact with the human host. The parasite regularly exchanges the expressed var gene generating antigenic variation of the infected RBCs (pRBC) surface which is crucial for successful proliferation and transmission. PfEMP1 is also an adhesive molecule that binds to an array of human receptors. By sequestration in the post-capillary venules, pRBCs are able to escape the spleen-mediated clearance but severe malaria may develop if the local binding is extensive. Anti-PfEMP1 immunity is important for preventing the development of both cerebral malaria and placental malaria, but more immunological studies on PfEMP1 antigens and their interaction with the human host are needed. Over the last few years our knowledge about var genes and PfEMP1s has increased dramatically through genetic, biochemical, immunological and epidemiological studies. In addition, the genome sequence has also provided us with a new platform for further dissecting its biological functions. This review highlights the recent analyses of var genes in the P. falciparum genome and postulates significance of genome recombination to the diversity of parasite virulence.

摘要

恶性疟原虫红细胞膜蛋白1(PfEMP1)是一种重要的毒力因子,由大约60个var基因家族编码,被疟原虫用来与人类宿主相互作用。疟原虫定期交换表达的var基因,产生受感染红细胞(pRBC)表面的抗原变异,这对于成功增殖和传播至关重要。PfEMP1也是一种粘附分子,可与一系列人类受体结合。通过在毛细血管后微静脉中滞留,pRBC能够逃避脾脏介导的清除,但如果局部结合广泛,则可能发展为严重疟疾。抗PfEMP1免疫对于预防脑型疟疾和胎盘疟疾的发展都很重要,但需要对PfEMP1抗原及其与人类宿主的相互作用进行更多的免疫学研究。在过去几年中,通过遗传、生化、免疫和流行病学研究,我们对var基因和PfEMP1的了解有了显著增加。此外,基因组序列也为我们进一步剖析其生物学功能提供了一个新平台。本综述重点介绍了恶性疟原虫基因组中var基因的最新分析,并推测了基因组重组对寄生虫毒力多样性的意义。

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