| Autor: |
Hannah C Lewis, Laurel E Kelnhofer-Millevolte, Mia R Brinkley, Hannah E Arbach, Edward A Arnold, Srinivas Ramachandran, Daphne C Avgousti |
| Rok vydání: |
2022 |
| DOI: |
10.1101/2022.05.31.494218 |
| Popis: |
Herpes simplex virus (HSV-1) progeny form in the nucleus and must exit to successfully infect other cells. These newly formed viral capsids navigate the complex chromatin architecture of the nucleus to reach the inner nuclear membrane and egress. Here, we demonstrate by transmission electron microscopy (TEM) that HSV-1 capsids traverse dense heterochromatin in the nuclear periphery to reach the inner nuclear membrane. We found that this heterochromatin is dependent on the specific chromatin marks of trimethylation on histone H3 lysine 27 (H3K27me3) and the histone variant macroH2A1. Through chromatin profiling over the course of infection, we revealed massive host genomic regions bound by macroH2A1 and H3K27me3 that correlate with decreased host transcription in active compartments. This indicates the formation of new heterochromatin during infection. We found that loss of these markers resulted in significantly lower viral titers but did not impact viral genome or protein accumulation. Strikingly, we discovered by TEM that loss of macroH2A1 or H3K27me3 resulted in nuclear trapping of viral capsids. Thus, our work demonstrates that HSV-1 takes advantage of the dynamic nature of host heterochromatin formation during infection for efficient viral egress. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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