Barnes D A, Bonnin A, Huang J X, Gousset L, Wu J, Gut J, Doyle P, Dubremetz J F, Ward H, Petersen C
Department of Medicine, University of California-San Francisco General Hospital, 94110, USA.
Mol Biochem Parasitol. 1998 Oct 30;96(1-2):93-110. doi: 10.1016/s0166-6851(98)00119-4.
Cryptosporidium parvum is a protozoan parasite which produces self-limited disease in immunocompetent hosts and devastating, persistent diarrhea in immunocompromised individuals. There is no effective treatment for cryptosporidiosis and little is known about the basic biology of the organism. Cloning and sequence analysis of the gene encoding GP900, a previously identified > 900 kDa glycoprotein, predicts a mucin-like glycoprotein composed of distal cysteine-rich domains separated by polythreonine domains and a large membrane proximal N-glycosylated core region. A trinucleotide repeat composed predominantly of the triplet ACA encodes the threonine domains. GP900 is stored in micronemes prior to appearance on the surface of invasive forms. The concentration of native GP900 which inhibits 50% (IC50) of invasion in vitro is low picomolar; the IC50 for a recombinant cysteine rich-domain is low nanomolar. These observations indicate that GP900 is a parasite ligand for a host receptor involved in attachment/invasion and suggest that immunotherapy or chemotherapy directed against GP900 may be feasible.
微小隐孢子虫是一种原生动物寄生虫，它在免疫功能正常的宿主中引发自限性疾病，而在免疫功能低下的个体中则导致严重的持续性腹泻。隐孢子虫病尚无有效的治疗方法，人们对该生物体的基本生物学特性了解甚少。对先前鉴定出的分子量大于900 kDa的糖蛋白GP900编码基因进行克隆和序列分析，预测其为一种黏蛋白样糖蛋白，由富含半胱氨酸的远端结构域和聚苏氨酸结构域分隔，以及一个大的膜近端N-糖基化核心区域组成。主要由三联体ACA组成的三核苷酸重复序列编码苏氨酸结构域。GP900在侵袭性形式的表面出现之前储存在微线体中。抑制体外侵袭50%（IC50）的天然GP900浓度为低皮摩尔；富含半胱氨酸重组结构域的IC50为低纳摩尔。这些观察结果表明，GP900是参与附着/侵袭的宿主受体的寄生虫配体，并提示针对GP900的免疫疗法或化学疗法可能是可行的。
