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Diverse Viruses Require the Calcium Transporter SPCA1 for Maturation and Spread
Cell Host & Microbe ( IF 30.3 ) Pub Date : 2017-10-11 , DOI: 10.1016/j.chom.2017.09.002
H.-Heinrich Hoffmann , William M. Schneider , Vincent A. Blomen , Margaret A. Scull , Alain Hovnanian , Thijn R. Brummelkamp , Charles M. Rice

Respiratory and arthropod-borne viral infections are a global threat due to the lack of effective antivirals and vaccines. A potential strategy is to target host proteins required for viruses but non-essential for the host. To identify such proteins, we performed a genome-wide knockout screen in human haploid cells and identified the calcium pump SPCA1. SPCA1 is required by viruses from the Paramyxoviridae, Flaviviridae, and Togaviridae families, including measles, dengue, West Nile, Zika, and chikungunya viruses. Calcium transport activity is required for SPCA1 to promote virus spread. SPCA1 regulates proteases within the trans-Golgi network that require calcium for their activity and are critical for virus glycoprotein maturation. Consistent with these findings, viral glycoproteins fail to mature in SPCA1-deficient cells preventing viral spread, which is evident even in cells with partial loss of SPCA1. Thus, SPCA1 is an attractive antiviral host target for a broad spectrum of established and emerging viral infections.



中文翻译:

多种病毒需要钙转运蛋白SPCA1才能成熟和扩散

由于缺乏有效的抗病毒剂和疫苗,呼吸道和节肢动物传播的病毒感染是全球性威胁。一种潜在的策略是靶向病毒所需但宿主非必需的宿主蛋白。为了鉴定此类蛋白质,我们在人类单倍体细胞中进行了全基因组敲除筛选,并鉴定了钙泵SPCA1。SPCA1是由病毒所需的副黏病毒科黄病毒,和披膜病毒科,包括麻疹,登革热,西尼罗河病毒,寨卡,和基孔肯雅病毒。钙转运活性是SPCA1促进病毒传播所必需的。SPCA1调节反式内的蛋白酶高尔基网络需要钙才能发挥其活性,并且对于病毒糖蛋白的成熟至关重要。与这些发现一致的是,病毒糖蛋白无法在SPCA1缺陷型细胞中成熟,从而阻止了病毒的传播,即使在部分丢失SPCA1的细胞中也很明显。因此,SPCA1是广泛的已建立和正在出现的病毒感染的有吸引力的抗病毒宿主靶标。

更新日期:2017-10-11
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