Journal Article

PUBDB-2024-00335

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png HSV-1 exploits host heterochromatin for nuclear egress

Lewis, H. C. ; Kelnhofer-Millevolte, L. E. ; Brinkley, M. R. ; Arbach, H. E. ; Arnold, E. A. ; Sanders, S.Extern*CSSB* ; Bosse, J. B.Extern*CSSB* ; Ramachandran, S. (Corresponding author) ; Avgousti, D. C. (Corresponding author)

2023
Rockefeller Univ. Press New York, NY

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Please use a persistent id in citations: doi:10.1083/jcb.202304106  doi:10.3204/PUBDB-2024-00335

Abstract: Herpes 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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Contributing Institute(s):

1. CSSB-MHH-JB (CSSB-MHH-JB)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)
2. DFG project 390874280 - EXC 2155: RESIST - Resolving Infection Susceptibility (390874280) (390874280)
3. DFG project 443644894 - FOR 5200: Disrupt - Evade - Exploit: Steuerung der Genexpression und Wirtsantwort durch DNA Viren (DEEP-DV) (443644894) (443644894)

Experiment(s):

1. No specific instrument

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Database coverage:
; ; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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