Chimeric Plasmodium falciparum parasites expressing Plasmodium vivax circumsporozoite protein fail to produce salivary gland sporozoites.
Chimeric Plasmodium falciparum parasites expressing Plasmodium vivax circumsporozoite protein fail to produce salivary gland sporozoites.
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DOI：
10.1186/s12936-018-2431-1
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发表时间：
2018-08-09
期刊：
影响因子：
3
通讯作者：
Khan SM
中科院分区：
文献类型：
--
作者：
Marin-Mogollon C;van Pul FJA;Miyazaki S;Imai T;Ramesar J;Salman AM;Winkel BMF;Othman AS;Kroeze H;Chevalley-Maurel S;Reyes-Sandoval A;Roestenberg M;Franke-Fayard B;Janse CJ;Khan SM
将编码环子孢子蛋白（CSP）的基因已被来自人疟疾寄生虫恶性疟原虫或间日疟原虫的csp基因替换的啮齿类疟疾寄生虫用作临床前工具以在体内评价CSP疫苗。这些嵌合啮齿动物寄生虫在斯氏按蚊中产生子孢子，其能够感染啮齿动物和人肝细胞。其中pfcsp基因已被pvcsp取代的嵌合恶性疟原虫寄生虫的可用性将开辟使用受控的人类疟疾感染研究在小规模临床试验中测试间日疟原虫CSP疫苗的可能性。使用CRISPR/Cas9基因编辑产生了两种嵌合恶性疟原虫寄生虫，其中pfcsp基因已被两种主要pvcsp等位基因VK 210或VK 247中的任一种替换。此外，还产生了缺乏CSP表达的恶性疟原虫寄生虫系。这些寄生虫系已被分析的子孢子生产在一个。斯蒂芬蚊子。两个嵌合Pf-PvCSP系在体外表现出正常的无性和有性血液阶段发育，并在An中产生含子孢子的卵囊。斯蒂芬蚊子。在卵囊衍生的Pf-PvCSP子孢子中证实了相应PvCSP的表达。然而，大多数卵囊在子孢子形成之前退化，并且在蚊子血腔或唾液腺中未发现子孢子。与嵌合Pf-PvCSP寄生虫不同，缺乏CSP表达的恶性疟原虫寄生虫的卵囊不产生子孢子。表达间日疟原虫环子孢子蛋白的嵌合恶性疟原虫不能产生唾液腺子孢子。结合起来，这些研究表明，虽然PvCSP可以部分地补充PfCSP的功能，CSP的物种特异性特征在两种人类疟疾寄生虫中控制完整的子孢子成熟和发育。本文的在线版本（10.1186/s12936-018-2431-1）包含补充材料，可供授权用户使用。
Rodent malaria parasites where the gene encoding circumsporozoite protein (CSP) has been replaced with csp genes from the human malaria parasites, Plasmodium falciparum or Plasmodium vivax, are used as pre-clinical tools to evaluate CSP vaccines in vivo. These chimeric rodent parasites produce sporozoites in Anopheles stephensi mosquitoes that are capable of infecting rodent and human hepatocytes. The availability of chimeric P. falciparum parasites where the pfcsp gene has been replaced by the pvcsp would open up possibilities to test P. vivax CSP vaccines in small scale clinical trials using controlled human malaria infection studies. Using CRISPR/Cas9 gene editing two chimeric P. falciparum parasites, were generated, where the pfcsp gene has been replaced by either one of the two major pvcsp alleles, VK210 or VK247. In addition, a P. falciparum parasite line that lacks CSP expression was also generated. These parasite lines have been analysed for sporozoite production in An. stephensi mosquitoes. The two chimeric Pf-PvCSP lines exhibit normal asexual and sexual blood stage development in vitro and produce sporozoite-containing oocysts in An. stephensi mosquitoes. Expression of the corresponding PvCSP was confirmed in oocyst-derived Pf-PvCSP sporozoites. However, most oocysts degenerate before sporozoite formation and sporozoites were not found in either the mosquito haemocoel or salivary glands. Unlike the chimeric Pf-PvCSP parasites, oocysts of P. falciparum parasites lacking CSP expression do not produce sporozoites. Chimeric P. falciparum parasites expressing P. vivax circumsporozoite protein fail to produce salivary gland sporozoites. Combined, these studies show that while PvCSP can partially complement the function of PfCSP, species-specific features of CSP govern full sporozoite maturation and development in the two human malaria parasites. The online version of this article (10.1186/s12936-018-2431-1) contains supplementary material, which is available to authorized users.
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影响因子：
5.4
作者：
Long CA;Zavala F
通讯作者：
Zavala F
影响因子：
14.9
作者：
Deitsch, KW;Driskill, CL;Wellems, TE
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影响因子：
3.1
作者：
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影响因子：
46.9
作者：
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通讯作者：
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