Retrovirus infection strongly enhances scrapie infectivity release in cell culture
Retrovirus infection strongly enhances scrapie infectivity release in cell culture
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DOI：
10.1038/sj.emboj.7601162
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发表时间：
2006-06-21
期刊：
影响因子：
11.4
通讯作者：
Darlix, Jean Luc
中科院分区：
文献类型：
--
作者：
Leblanc, Pascal;Alais, Sandrine;Darlix, Jean Luc
Prion病是一种神经退行性疾病，在大多数情况下与PrPSc(构象改变的细胞PrPC异构体；SC表示瘙痒病)在中枢神经系统积聚有关，PrPSc是PrPC的一种部分抗蛋白酶亚型。PrPSc被认为是传染性海绵状脑病的病原体。PrPSc的细胞间转移机制仍是个谜。最近，在细胞培养模型中，被称为外体的小细胞内体来源的小囊泡被认为有助于普恩的传播。逆转录病毒，如小鼠白血病病毒(MuLV)或人类免疫缺陷病毒1型(HIV-1)，已被证明可以组装和萌发到耐洗涤剂的微域和细胞内的隔间，如晚期内体/多囊体。在这里，我们报告了Moloney鼠白血病病毒(MoMuLV)感染强烈地促进了混合感染细胞上清液中的瘙痒病传染性的释放。在此条件下，我们发现PrPc、PrPSc和瘙痒病的感染性都被MuLV病毒粒子和外体招募。我们认为逆转录病毒可能是病理性Pron病原体传播的重要辅助因素。
Prion diseases are neurodegenerative disorders associated in most cases with the accumulation in the central nervous system of PrPSc ( conformationally altered isoform of cellular prion protein ( PrPC); Sc for scrapie), a partially protease-resistant isoform of the PrPC. PrPSc is thought to be the causative agent of transmissible spongiform encephalopathies. The mechanisms involved in the intercellular transfer of PrPSc are still enigmatic. Recently, small cellular vesicles of endosomal origin called exosomes have been proposed to contribute to the spread of prions in cell culture models. Retroviruses such as murine leukemia virus ( MuLV) or human immunodeficiency virus type 1 ( HIV-1) have been shown to assemble and bud into detergent-resistant microdomains and into intracellular compartments such as late endosomes/multivesicular bodies. Here we report that moloney murine leukemia virus ( MoMuLV) infection strongly enhances the release of scrapie infectivity in the supernatant of coinfected cells. Under these conditions, we found that PrPC, PrPSc and scrapie infectivity are recruited by both MuLV virions and exosomes. We propose that retroviruses can be important cofactors involved in the spread of the pathological prion agent.