Gonzalez-Ceron L, Rodriguez M H, Wirtz R A, Sina B J, Palomeque O L, Nettel J A, Tsutsumi V
Centro de Investigación de Paludismo, Instituto Nacional de Salud Pública, 4 Norte and 19 Poniente, Tapachula, Chiapas, 30700, Mexico.
Exp Parasitol. 1998 Nov;90(3):203-11. doi: 10.1006/expr.1998.4334.
The major surface circumsporozoite (CS) proteins are known to play a role in malaria sporozoite development and invasion of invertebrate and vertebrate host cells. Plasmodium vivax CS protein processing during mosquito midgut oocyst and salivary gland sporozoite development was studied using monoclonal antibodies which recognize different CS protein epitopes. Monoclonal antibodies which react with the CS amino acid repeat sequences by ELISA recognized a 50-kDa precursor protein in immature oocyst and additional 47- and 42-kDa proteins in older oocysts. A 42-kDa CS protein was detected after initial sporozoite invasion of mosquito salivary glands and an additional 50-kDa precursor CS protein observed later in infected salivary glands. These data confirm previous results with other Plasmodium species, in which more CS protein precursors were detected in oocysts than in salivary gland sporozoites. A monoclonal antibody (PvPCS) was characterized which reacts with an epitope found only in the 50-kDa precursor CS protein. PvPCS reacted with all P. vivax sporozoite strains tested by indirect immunofluorescent assay, homogeneously staining the sporozoite periphery with much lower intensity than that produced by anti-CS repeat antibodies. Immunoelectron microscopy using PvPCS showed that the CS protein precursor was associated with peripheral cytoplasmic vacuoles and membranes of sporoblast and budding sporozoites in development oocysts. In salivary gland sporozoites, the CS protein precursor was primarily associated with micronemes and sporozoite membranes. Our results suggest that the 50-kDa CS protein precursor is synthesized intracellularly and secreted on the membrane surface, where it is proteolytically processed to form the 42-kDa mature CS protein. These data indicate that differences in CS protein processing in oocyst and salivary gland sporozoites development may occur.
主要的表面环子孢子(CS)蛋白已知在疟原虫子孢子发育以及对无脊椎动物和脊椎动物宿主细胞的入侵中发挥作用。利用识别不同CS蛋白表位的单克隆抗体,研究了间日疟原虫CS蛋白在蚊子中肠卵囊和唾液腺子孢子发育过程中的加工情况。通过酶联免疫吸附测定法与CS氨基酸重复序列发生反应的单克隆抗体,在未成熟卵囊中识别出一种50 kDa的前体蛋白,在较老的卵囊中识别出另外47 kDa和42 kDa的蛋白。在子孢子最初侵入蚊子唾液腺后检测到一种42 kDa的CS蛋白,之后在受感染的唾液腺中观察到另外一种50 kDa的前体CS蛋白。这些数据证实了之前对其他疟原虫物种的研究结果,即在卵囊中检测到的CS蛋白前体比在唾液腺子孢子中更多。鉴定出一种单克隆抗体(PvPCS),它与仅在50 kDa的前体CS蛋白中发现的一个表位发生反应。通过间接免疫荧光测定法,PvPCS与所有测试的间日疟原虫子孢子株发生反应,以比抗CS重复抗体产生的强度低得多的强度均匀地染色子孢子周边。使用PvPCS的免疫电子显微镜显示,CS蛋白前体与发育中卵囊内的成孢子细胞和出芽子孢子的周边细胞质空泡及膜相关。在唾液腺子孢子中,CS蛋白前体主要与微线体和子孢子膜相关。我们的结果表明,50 kDa的CS蛋白前体在细胞内合成并分泌到膜表面,在那里它被蛋白酶加工形成42 kDa的成熟CS蛋白。这些数据表明,卵囊和唾液腺子孢子发育过程中CS蛋白加工可能存在差异。