Cytoplasmic control of intranuclear polarity by human cytomegalovirus

Abstract

Despite its size and rigidity, the nucleus is moved or reorganized by cytoskeletal filaments under various conditions 1 – 11 . Moreover, while chromatin organize into non-random domains 12 , extensive heterogeneity at the single-cell level 13 means that precisely how and why nuclei reorganize remains an area of intense investigation. Here, we developed convolutional neural network (CNN)-based automated cell classification and analysis pipelines which revealed the extent to which human cytomegalovirus (HCMV) generates nuclear polarity through a virus-assembled microtubule-organizing center (MTOC). Tubulin acetylation enables microtubules emanating from this MTOC to rotate the nucleus via cytoplasmically exposed dynein-binding domains in the outer nuclear membrane protein, Nesprin-2G, which polarizes the inner nuclear membrane protein, SUN1. This in turn creates intranuclear polarity in Emerin to control nuclear actin filaments that spatially segregate viral DNA from inactive histones and host DNA, maximizing virus replication. Our findings uncover the extent to which viruses can control the nucleus from the cytoplasm.

Negative charge in the RACK1 loop broadens the translational capacity of the human ribosome

“…For single cell RFP and GFP intensity measurements, randomized images were entered into the CellProfiler pipeline ( McQuin et al, 2018 ; Procter et al, 2020 ) and resized to 256×256 pixels. The pipeline was used to identify target objects using the images in the RFP channel.…”

Regulation of the MIE Locus During HCMV Latency and Reactivation

“…These proteins do not directly bind the MIE locus, but rather they impart their effects through upstream control. Furthermore, recent findings suggest HCMV reorganizes inactive histones and cellular DNA, thereby isolating the viral genome to optimize viral gene transcription and replication [254]. Collectively, these suggest the cellular environment plays a large role in controlling MIE-mediated transcription and therefore the stage of infection.…”

mSphere of Influence: Viruses—Pathogens or Expert Cell Biologists?

“…As viruses have evolved with their hosts for thousands of years, examining how they either utilize or avoid cellular factors to promote infection has often been the basis of new scientific knowledge and discovery. In these two papers, Procter et al demonstrate just that through their investigation of how another important human pathogen, human cytomegalovirus (HCMV), manipulates the cell during infection ( 1 , 2 ).…”

“…In order to further investigate this virus-induced phenomenon, Procter et al ( 2 ) developed convolutional neural network (CNN)-based automated cell classification and analysis pipelines to measure the spatial organization of thousands of individual cells. The authors found that acetylated MTs generated at the viral AC interact with linker of nucleoskeleton and cytoskeleton (LINC) complexes in the nuclear membrane to rotate the nucleus through cytoplasmic dynein motor binding domains in Nesprin-2.…”