近年來(lái)的研究表明,小腸原生動(dòng)物寄生蟲(chóng)藍(lán)氏賈第鞭毛蟲(chóng)表面抗原的變異與致病作用有關(guān), 甚至于變異快的蟲(chóng)株可不受宿主免疫應(yīng)答的影響, 從而更有利于蟲(chóng)體在宿主小腸內(nèi)寄生,。不同蟲(chóng)株及相同蟲(chóng)株表達(dá)不同表面抗原的克隆之間的致病力也各不相同,。藍(lán)氏賈第鞭毛蟲(chóng)通過(guò)抗原變異來(lái)躲避宿主免疫系統(tǒng),，即一次只表達(dá)很多“變異體表面蛋白”（VSPs）中的一個(gè),，并通過(guò)一個(gè)未知機(jī)制自發(fā)切換VSPs。
VSP是一種多態(tài)蛋白, 包裹在整個(gè)寄生蟲(chóng)滋養(yǎng)體的表面, 該抗原在誘導(dǎo)宿主的保護(hù)性免疫反應(yīng),、激活免疫細(xì)胞,、抑制乃至殺死蟲(chóng)體的免疫效應(yīng)中, 都具有很重要的作用。體內(nèi)和體外實(shí)驗(yàn)均證明, 該蛋白分子在不同時(shí)間內(nèi)表達(dá)出不同類型的蛋白分子,。因此, 人們將此抗原稱為變異特異性表面蛋白( variant-specificurface protein,VSP)。
在最新一期Nature中,，阿根廷科學(xué)家Prucca等人發(fā)現(xiàn),，VSP表達(dá)由該寄生蟲(chóng)的RNA干涉系統(tǒng)調(diào)控。將Dicer和依賴于RNA的RNA聚合酶（RNA干涉系統(tǒng)的兩個(gè)組成部分）沉默，會(huì)誘導(dǎo)多VSP表達(dá),，并使對(duì)抗體的易感性增大,。這一發(fā)現(xiàn)對(duì)于有關(guān)賈第鞭毛蟲(chóng)病疫苗的研究工作有很大幫助。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
