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鼠多瘤病毒 DNA 在感染过程中通过空间上不同的核复制亚区进行转换。

Murine polyomavirus DNA transitions through spatially distinct nuclear replication subdomains during infection.

机构信息

Department of Molecular, Cellular, and Developmental Biology, University of Colorado Boulder, Boulder, Colorado, United States of America.

BioFrontiers Institute, University of Colorado Boulder, Boulder, Colorado, United States of America.

出版信息

PLoS Pathog. 2020 Mar 23;16(3):e1008403. doi: 10.1371/journal.ppat.1008403. eCollection 2020 Mar.

DOI:10.1371/journal.ppat.1008403
PMID:32203554
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7117779/
Abstract

The replication of small DNA viruses requires both host DNA replication and repair factors that are often recruited to subnuclear domains termed viral replication centers (VRCs). Aside from serving as a spatial focus for viral replication, little is known about these dynamic areas in the nucleus. We investigated the organization and function of VRCs during murine polyomavirus (MuPyV) infection using 3D structured illumination microscopy (3D-SIM). We localized MuPyV replication center components, such as the viral large T-antigen (LT) and the cellular replication protein A (RPA), to spatially distinct subdomains within VRCs. We found that viral DNA (vDNA) trafficked sequentially through these subdomains post-synthesis, suggesting their distinct functional roles in vDNA processing. Additionally, we observed disruption of VRC organization and vDNA trafficking during mutant MuPyV infections or inhibition of DNA synthesis. These results reveal a dynamic organization of VRC components that coordinates virus replication.

摘要

小 DNA 病毒的复制需要宿主 DNA 复制和修复因子，这些因子通常被招募到称为病毒复制中心 (VRC) 的亚核域。除了作为病毒复制的空间焦点外，对于细胞核中这些动态区域知之甚少。我们使用三维结构照明显微镜 (3D-SIM) 研究了小鼠多瘤病毒 (MuPyV) 感染期间 VRC 的组织和功能。我们将 MuPyV 复制中心组件（如病毒大 T 抗原 (LT) 和细胞复制蛋白 A (RPA)）定位到 VRC 内空间上不同的亚域。我们发现病毒 DNA (vDNA) 在合成后依次通过这些亚域运输，表明它们在 vDNA 处理中具有不同的功能作用。此外，我们观察到 VRC 组织和 vDNA 运输在突变 MuPyV 感染或 DNA 合成抑制期间中断。这些结果揭示了协调病毒复制的 VRC 组件的动态组织。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/544a/7117779/5dcbcdac3b0c/ppat.1008403.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/544a/7117779/279c8d5fb5b7/ppat.1008403.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/544a/7117779/3da2712992a5/ppat.1008403.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/544a/7117779/de33c3423771/ppat.1008403.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/544a/7117779/21236640686c/ppat.1008403.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/544a/7117779/6cfb5fad05ac/ppat.1008403.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/544a/7117779/da142b4d9aeb/ppat.1008403.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/544a/7117779/67a026f9a500/ppat.1008403.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/544a/7117779/5dcbcdac3b0c/ppat.1008403.g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/544a/7117779/279c8d5fb5b7/ppat.1008403.g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/544a/7117779/3da2712992a5/ppat.1008403.g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/544a/7117779/de33c3423771/ppat.1008403.g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/544a/7117779/21236640686c/ppat.1008403.g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/544a/7117779/6cfb5fad05ac/ppat.1008403.g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/544a/7117779/da142b4d9aeb/ppat.1008403.g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/544a/7117779/67a026f9a500/ppat.1008403.g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/544a/7117779/5dcbcdac3b0c/ppat.1008403.g008.jpg

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