Laboratory of Virology and Infectious Disease, The Rockefeller University, New York, NY 10065, USA.
Biochemistry Division, Netherlands Cancer Institute, 1066 CX Amsterdam, The Netherlands.
Cell Host Microbe. 2017 Oct 11;22(4):460-470.e5. doi: 10.1016/j.chom.2017.09.002.
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.
呼吸道和节肢动物传播的病毒感染是一个全球性的威胁，因为缺乏有效的抗病毒药物和疫苗。一种潜在的策略是针对宿主蛋白，这些蛋白是病毒所必需的，但对宿主是非必需的。为了鉴定这些蛋白，我们在人类单倍体细胞中进行了全基因组敲除筛选，鉴定出钙泵 SPCA1。SPCA1 是副粘病毒科、黄病毒科和披膜病毒科病毒所必需的，包括麻疹、登革热、西尼罗河、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 调节高尔基体内的蛋白酶，这些蛋白酶的活性需要钙，对于病毒糖蛋白成熟至关重要。与这些发现一致的是，SPCA1 缺陷细胞中的病毒糖蛋白无法成熟，从而阻止了病毒的传播，即使在 SPCA1 部分缺失的细胞中也是如此。因此，SPCA1 是一种有吸引力的抗病毒宿主靶标，可用于广泛的已建立和新兴的病毒感染。
