In vivo pair correlation microscopy reveals dengue virus capsid protein nucleocytoplasmic bidirectional movement in mammalian infected cells.
In vivo pair correlation microscopy reveals dengue virus capsid protein nucleocytoplasmic bidirectional movement in mammalian infected cells.
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DOI：
10.1038/s41598-021-03854-z
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发表时间：
2021-12-24
影响因子：
4.6
通讯作者：
Estrada LC
中科院分区：
文献类型：
--
作者：
Sallaberry I;Luszczak A;Philipp N;Navarro GSC;Gabriel MV;Gratton E;Gamarnik AV;Estrada LC
黄病毒是引起人类疾病的主要病原体，包括登革热病毒、寨卡病毒、黄热病病毒等。DENV每年感染全世界数亿人，造成巨大的社会和经济负担。DENV衣壳(C)蛋白在基因组衣壳化和病毒颗粒形成过程中起重要作用。以前已经证明，DENV C进入感染细胞的细胞核。然而，DENV C蛋白是否表现出核输出尚不清楚。通过空间交叉关联细胞的不同区域，我们研究了感染周期中DENV - C在核膜上的运动。我们观察到运输发生在两个方向上，并且具有相似的易位时间（以毫秒为时间尺度），这表明C蛋白的输入和输出都是双向的。此外，从细胞质区和核区对互相关函数中，我们发现每个室中有两个C分子群体具有快速和缓慢的移动。在细胞质中，快迁移种群和慢迁移种群的相关时间分别为2 ~ 6 ms和40 ~ 110 ms；在细胞核中，相关时间分别为1 ~ 10 ms和25 ~ 140 ms。DENV C在细胞质和核区的快速迁移与先前相关分析中报道的布朗运动扩散系数一致。这些研究提供了DENV C在感染细胞内穿梭于细胞核之间的第一个证据，为抗病毒干预开辟了新的场所。
Flaviviruses are major human disease-causing pathogens, including dengue virus (DENV), Zika virus, yellow fever virus and others. DENV infects hundreds of millions of people per year around the world, causing a tremendous social and economic burden. DENV capsid (C) protein plays an essential role during genome encapsidation and viral particle formation. It has been previously shown that DENV C enters the nucleus in infected cells. However, whether DENV C protein exhibits nuclear export remains unclear. By spatially cross-correlating different regions of the cell, we investigated DENV C movement across the nuclear envelope during the infection cycle. We observed that transport takes place in both directions and with similar translocation times (in the ms time scale) suggesting a bidirectional movement of both C protein import and export. Furthermore, from the pair cross-correlation functions in cytoplasmic or nuclear regions we found two populations of C molecules in each compartment with fast and slow mobilities. While in the cytoplasm the correlation times were in the 2–6 and 40–110 ms range for the fast and slow mobility populations respectively, in the cell nucleus they were 1–10 and 25–140 ms range, respectively. The fast mobility of DENV C in cytoplasmic and nuclear regions agreed with the diffusion coefficients from Brownian motion previously reported from correlation analysis. These studies provide the first evidence of DENV C shuttling from and to the nucleus in infected cells, opening new venues for antiviral interventions.
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DOI：
10.1111/tra.12305
发表时间：
2015-09
期刊：
Traffic (Copenhagen, Denmark)
影响因子：
--
作者：
Iglesias NG;Mondotte JA;Byk LA;De Maio FA;Samsa MM;Alvarez C;Gamarnik AV
通讯作者：
Gamarnik AV
DOI：
10.1073/pnas.1006731107
发表时间：
2010-09-21
影响因子：
11.1
作者：
Hinde, Elizabeth;Cardarelli, Francesco;Gratton, Enrico
通讯作者：
Gratton, Enrico
DOI：
10.1083/jcb.200411005
发表时间：
2005-01-17
期刊：
The Journal of cell biology
影响因子：
--
作者：
Kubitscheck U;Grünwald D;Hoekstra A;Rohleder D;Kues T;Siebrasse JP;Peters R
通讯作者：
Peters R
影响因子：
3.4
作者：
Malacrida, Leonel;Hedde, Per Niklas;Gratton, Enrico
通讯作者：
Gratton, Enrico
影响因子：
3.8
作者：
Sangiambut, Sutha;Keelapang, Poonsook;Sittisombut, Nopporn
通讯作者：
Sittisombut, Nopporn