The nairovirus nairobi sheep disease virus/ganjam virus induces the translocation of protein disulphide isomerase-like oxidoreductases from the endoplasmic reticulum to the cell surface and the extracellular space.

The nairovirus nairobi sheep disease virus/ganjam virus induces the translocation of protein disulphide isomerase-like oxidoreductases from the endoplasmic reticulum to the cell surface and the extracellular space.
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DOI:
10.1371/journal.pone.0094656
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发表时间:
2014
期刊:
影响因子:
3.7
通讯作者:
Baron MD
Baron MD
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Lasecka L;Baron MD

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奈洛病毒属的内罗毕绵羊病病毒(NSDV)引起绵羊和山羊的出血性胃肠炎,死亡率高达90%;该病毒发现于东非和中非以及印度,在印度该病毒被称为甘贾姆病毒。NSDV与人类病原体克里米亚-刚果出血热病毒密切相关,后者也会导致出血性疾病。与其他内罗病毒一样,NSDV的复制发生在细胞质中,新的病毒颗粒出芽进入高尔基体;然而,病毒复制对细胞区室的影响尚未得到广泛研究。我们已经发现,内质网(ER)的整体结构,ER-高尔基体中间室和高尔基体不受感染NSDV。然而,我们观察到,NSDV感染导致蛋白质二硫化物异构酶(PDI)的损失,氧化还原酶存在于内质网(ER)的内腔,并在蛋白质折叠过程中,从ER。进一步的研究表明,NSDV感染的细胞在其表面具有高水平的PDI,并且PDI也分泌到感染细胞的培养基中。来自PDI家族的另一种伴侣蛋白ERp 57被发现受到类似的影响。感染细胞和单个病毒糖蛋白表达的分析表明,NSDV PreGn糖蛋白参与这些可溶性ER氧化还原酶的再分布。已经表明,细胞外PDI可以激活整合素和组织因子,其分别参与促炎反应和弥散性血管内凝血,这两者都在许多病毒性出血热中表现出来。从NSDV感染的细胞中发现增强的PDI分泌可能是理解出血性内罗病毒致病性机制的重要发现。
Nairobi sheep disease virus (NSDV) of the genus Nairovirus causes a haemorrhagic gastroenteritis in sheep and goats with mortality up to 90%; the virus is found in East and Central Africa, and in India, where the virus is called Ganjam virus. NSDV is closely related to the human pathogen Crimean-Congo haemorrhagic fever virus, which also causes a haemorrhagic disease. As with other nairoviruses, replication of NSDV takes place in the cytoplasm and the new virus particles bud into the Golgi apparatus; however, the effect of viral replication on cellular compartments has not been studied extensively. We have found that the overall structure of the endoplasmic reticulum (ER), the ER-Golgi intermediate compartment and the Golgi were unaffected by infection with NSDV. However, we observed that NSDV infection led to the loss of protein disulphide isomerase (PDI), an oxidoreductase present in the lumen of the endoplasmic reticulum (ER) and which assists during protein folding, from the ER. Further investigation showed that NSDV-infected cells have high levels of PDI at their surface, and PDI is also secreted into the culture medium of infected cells. Another chaperone from the PDI family, ERp57, was found to be similarly affected. Analysis of infected cells and expression of individual viral glycoproteins indicated that the NSDV PreGn glycoprotein is involved in redistribution of these soluble ER oxidoreductases. It has been suggested that extracellular PDI can activate integrins and tissue factor, which are involved respectively in pro-inflammatory responses and disseminated intravascular coagulation, both of which manifest in many viral haemorrhagic fevers. The discovery of enhanced PDI secretion from NSDV-infected cells may be an important finding for understanding the mechanisms underlying the pathogenicity of haemorrhagic nairoviruses.
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