近年来的研究表明,小肠原生动物寄生虫蓝氏贾第鞭毛虫表面抗原的变异与致病作用有关, 甚至于变异快的虫株可不受宿主免疫应答的影响, 从而更有利于虫体在宿主小肠内寄生。不同虫株及相同虫株表达不同表面抗原的克隆之间的致病力也各不相同。蓝氏贾第鞭毛虫通过抗原变异来躲避宿主免疫系统,即一次只表达很多“变异体表面蛋白”(VSPs)中的一个,并通过一个未知机制自发切换VSPs。
VSP是一种多态蛋白, 包裹在整个寄生虫滋养体的表面, 该抗原在诱导宿主的保护性免疫反应、激活免疫细胞、抑制乃至杀死虫体的免疫效应中, 都具有很重要的作用。体内和体外实验均证明, 该蛋白分子在不同时间内表达出不同类型的蛋白分子。因此, 人们将此抗原称为变异特异性表面蛋白( variant-specificurface protein,VSP)。
在最新一期Nature中,阿根廷科学家Prucca等人发现,VSP表达由该寄生虫的RNA干涉系统调控。将Dicer和依赖于RNA的RNA聚合酶(RNA干涉系统的两个组成部分)沉默,会诱导多VSP表达,并使对抗体的易感性增大。这一发现对于有关贾第鞭毛虫病疫苗的研究工作有很大帮助。(生物谷Bioon.com)
生物谷推荐原始出处:
Nature 456, 750-754 (11 December 2008) | doi:10.1038/nature07585
Antigenic variation in Giardia lamblia is regulated by RNA interference
César G. Prucca1,2, Ileana Slavin1,2, Rodrigo Quiroga1, Eliana V. Elías1, Fernando D. Rivero1, Alicia Saura1, Pedro G. Carranza1 & Hugo D. Luján1
1 Laboratorio de Bioquímica y Biología Molecular, Facultad de Medicina, Universidad Católica de Córdoba, Córdoba X5004ASK, Argentina
2 These authors contributed equally to this work.
Giardia lamblia (also called Giardia intestinalis) is one of the most common intestinal parasites of humans. To evade the host's immune response, Giardia undergoes antigenic variation—a process that allows the parasite to develop chronic and recurrent infections. From a repertoire of 190 variant-specific surface protein (VSP)-coding genes, Giardia expresses only one VSP on the surface of each parasite at a particular time, but spontaneously switches to a different VSP by unknown mechanisms. Here we show that regulation of VSP expression involves a system comprising RNA-dependent RNA polymerase, Dicer and Argonaute, known components of the RNA interference machinery. Clones expressing a single surface antigen efficiently transcribe several VSP genes but only accumulate transcripts encoding the VSP to be expressed. Detection of antisense RNAs corresponding to the silenced VSP genes and small RNAs from the silenced but not for the expressed vsp implicate the RNA interference pathway in antigenic variation. Remarkably, silencing of Dicer and RNA-dependent RNA polymerase leads to a change from single to multiple VSP expression in individual parasites.