Open AccessCytoplasmic control of intranuclear polarity by human cytomegalovirus
Author(s) -
Dean J. Procter,
Colleen Furey,
Arturo G. Garza-Gongora,
Steven T. Kosak,
Derek Walsh
Publication year - 2020
Publication title -
nature
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 15.993
H-Index - 1226
eISSN - 1476-4687
pISSN - 0028-0836
DOI - 10.1038/s41586-020-2714-x
Subject(s) - microbiology and biotechnology , chromatin , cytoplasm , histone , biology , emerin , microtubule , cell nucleus , nuclear membrane , cytoskeleton , nucleus , cell polarity , inner membrane , nuclear transport , dna , cell , nuclear protein , genetics , gene , transcription factor , mitochondrion
Despite its size and rigidity, the cell nucleus can be moved or reorganized by cytoskeletal filaments under various conditions (for example, during viral infection) 1-11 . Moreover, whereas chromatin organizes 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 describe convolutional neural network-based automated cell classification and analysis pipelines, which revealed the extent to which human cytomegalovirus generates nuclear polarity through a virus-assembled microtubule-organizing centre. Acetylation of tubulin enables microtubules emanating from this centre to rotate the nucleus by engaging 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, and thereby controls nuclear actin filaments that spatially segregate viral DNA from inactive histones and host DNA, maximizing virus replication. Our findings demonstrate the extent to which viruses can control the nucleus from the cytoplasm.