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000601642 1001_ $$0P:(DE-HGF)0$$aLewis, Hannah C.$$b0
000601642 245__ $$aHSV-1 exploits host heterochromatin for nuclear egress
000601642 260__ $$aNew York, NY$$bRockefeller Univ. Press$$c2023
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000601642 520__ $$aHerpes simplex virus (HSV-1) progeny form in the nucleus and exit to successfully infect other cells. Newly formed capsids navigate complex chromatin architecture to reach the inner nuclear membrane (INM) and egress. Here, we demonstrate by transmission electron microscopy (TEM) that HSV-1 capsids traverse heterochromatin associated with trimethylation on histone H3 lysine 27 (H3K27me3) and the histone variant macroH2A1. Through chromatin profiling during infection, we revealed global redistribution of these marks whereby massive host genomic regions bound by macroH2A1 and H3K27me3 correlate with decreased host transcription in active compartments. We found that the loss of these markers resulted in significantly lower viral titers but did not impact viral genome or protein accumulation. Strikingly, we discovered that loss of macroH2A1 or H3K27me3 resulted in nuclear trapping of capsids. Finally, by live-capsid tracking, we quantified this decreased capsid movement. Thus, our work demonstrates that HSV-1 takes advantage of the dynamic nature of host heterochromatin formation during infection for efficient nuclear egress. 
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000601642 7001_ $$0P:(DE-HGF)0$$aKelnhofer-Millevolte, Laurel E.$$b1
000601642 7001_ $$0P:(DE-HGF)0$$aBrinkley, Mia R.$$b2
000601642 7001_ $$0P:(DE-HGF)0$$aArbach, Hannah E.$$b3
000601642 7001_ $$0P:(DE-HGF)0$$aArnold, Edward A.$$b4
000601642 7001_ $$0P:(DE-H253)PIP1093777$$aSanders, Saskia$$b5
000601642 7001_ $$0P:(DE-H253)PIP1082972$$aBosse, Jens Bernhard$$b6
000601642 7001_ $$0P:(DE-HGF)0$$aRamachandran, Srinivas$$b7$$eCorresponding author
000601642 7001_ $$0P:(DE-HGF)0$$aAvgousti, Daphne C.$$b8$$eCorresponding author
000601642 773__ $$0PERI:(DE-600)1421310-2$$a10.1083/jcb.202304106$$gVol. 222, no. 9, p. e202304106$$n9$$pe202304106$$tThe journal of cell biology$$v222$$x0021-9525$$y2023
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