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| Status |
Public on Jul 01, 2023 |
| Title |
HSV-1 exploits host heterochromatin for egress [CUT&Tag] |
| Organisms |
Homo sapiens; Human alphaherpesvirus 1 |
| Experiment type |
Genome binding/occupancy profiling by high throughput sequencing
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| Summary |
Herpes simplex virus replicates and forms progeny in the nucleus where it must overcome host chromatin to establish a successful infection. During lytic infection, newly formed viral capsids navigate through heterochromatin channels at the nuclear periphery to egress out of the nucleus. In uninfected cells, specific histone marks such as trimethylation on histone H3 lysine 27 (H3K27me3) and the histone variant macroH2A1 delineate heterochromatin regions, or repressed chromatin, that are predominantly located in the nuclear periphery. We examined these markers during HSV-1 lytic infection in primary cells and discovered a striking increase in the levels of macroH2A1 and H3K27me3. Here, we demonstrate that the loss of macroH2A1 results in significantly lower viral titers but does not impair viral transcription, protein production, or replication. By inhibiting the deposition of H3K27me3 by EZH2, we further show that reduction of H3K27me3 also leads to a significant decrease in viral titers. Through chromatin profiling via Cleavage Under Targets and tagmentation (CUT&Tag) of macroH2A1 and H3K27me3, we define the specific chromatin regions that change dynamically during HSV-1 lytic infection and show that regions with increased macroH2A1 and H3K27me3 correlate with decreased host transcription as measured by RNA-seq. Furthermore, we find by electron microscopy that loss of macroH2A1 results in reduced heterochromatin at the nuclear periphery and significantly more viral capsids trapped in the nuclear compartment. Using both high and low shedding clinical isolates of HSV-1, we similarly find that HSV-1 titers are significantly reduced in the absence of macroH2A1. Our work demonstrates that HSV-1 takes advantage of the dynamic nature of host heterochromatin formation during infection for efficient viral egress from the nuclear compartment.
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| Overall design |
Cleavage Under Targets and Tagmentation (CUT&Tag) for histone variant macroH2A1 and histone modification H3K27me3 during lytic Herpes Simplex Virus-1 infection in human foreskin fibroblasts both wild-type primary and tert-immortalized knocked out for macroH2A1.
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| Contributor(s) |
Lewis HC, Kelnhofer-Millevolte LE, Brinkley MR, Arbach HE, Arnold EA, Ramachandran S, Avgousti DC |
| Citation missing |
Has this study been published? Please login to update or notify GEO. |
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| Submission date |
Jul 13, 2022 |
| Last update date |
Jul 01, 2023 |
| Contact name |
Daphne Avgousti |
| Organization name |
Fred Hutchinson Cancer Research Center
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| Department |
Human Biology
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| Street address |
1100 Fairview Avenue North C1-201
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| City |
Seattle |
| State/province |
WA |
| ZIP/Postal code |
98109 |
| Country |
USA |
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| Platforms (1) |
| GPL23890 |
Illumina HiSeq 2500 (Homo sapiens; Human alphaherpesvirus 1) |
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| Samples (48)
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| GSM6337786 |
HFF, IgG, HSV-1 12 hpi, Rep2 |
| GSM6337787 |
HFF, IgG, Mock, Rep3 |
| GSM6337788 |
HFF, IgG, HSV-1 4 hpi, Rep3 |
| GSM6337789 |
HFF, IgG, HSV-1 8 hpi, Rep3 |
| GSM6337790 |
HFF, IgG, HSV-1 12 hpi, Rep3 |
| GSM6337791 |
HFF, H3K27me3, Mock, Rep2 |
| GSM6337792 |
HFF, H3K27me3, HSV-1 4 hpi, Rep2 |
| GSM6337793 |
HFF, H3K27me3, HSV-1 8 hpi, Rep2 |
| GSM6337794 |
HFF, H3K27me3, HSV-1 12 hpi, Rep2 |
| GSM6337795 |
HFF, H3K27me3, Mock, Rep3 |
| GSM6337796 |
HFF, H3K27me3, HSV-1 4 hpi, Rep3 |
| GSM6337797 |
HFF, H3K27me3, HSV-1 8 hpi, Rep3 |
| GSM6337798 |
HFF, H3K27me3, HSV-1 12 hpi, Rep3 |
| GSM6337799 |
HFF, macroH2A1, Mock, Rep2 |
| GSM6337800 |
HFF, macroH2A1, HSV-1 4 hpi, Rep2 |
| GSM6337801 |
HFF, macroH2A1, HSV-1 8 hpi, Rep2 |
| GSM6337802 |
HFF, macroH2A1, HSV-1 12 hpi, Rep2 |
| GSM6337803 |
HFF, macroH2A1, Mock, Rep3 |
| GSM6337804 |
HFF, macroH2A1, HSV-1 4 hpi, Rep3 |
| GSM6337805 |
HFF, macroH2A1, HSV-1 8 hpi, Rep3 |
| GSM6337806 |
HFF, macroH2A1, HSV-1 12 hpi, Rep3 |
| GSM6337807 |
KO, IgG, Mock, Rep2 |
| GSM6337808 |
KO, IgG, HSV-1 4 hpi, Rep2 |
| GSM6337809 |
KO, IgG, HSV-1 8 hpi, Rep2 |
| GSM6337810 |
KO, IgG, HSV-1 12 hpi, Rep2 |
| GSM6337811 |
KO, IgG, Mock, Rep3 |
| GSM6337812 |
KO, IgG, HSV-1 4 hpi, Rep3 |
| GSM6337813 |
KO, IgG, HSV-1 8 hpi, Rep3 |
| GSM6337814 |
KO, IgG, HSV-1 12 hpi, Rep3 |
| GSM6337815 |
KO, H3K27me3, Mock, Rep2 |
| GSM6337816 |
KO, H3K27me3, HSV-1 4 hpi, Rep2 |
| GSM6337817 |
KO, H3K27me3, HSV-1 8 hpi, Rep2 |
| GSM6337818 |
KO, H3K27me3, HSV-1 12 hpi, Rep2 |
| GSM6337819 |
KO, H3K27me3, Mock, Rep3 |
| GSM6337820 |
KO, H3K27me3, HSV-1 4 hpi, Rep3 |
| GSM6337821 |
KO, H3K27me3, HSV-1 8 hpi, Rep3 |
| GSM6337822 |
KO, H3K27me3, HSV-1 12 hpi, Rep3 |
| GSM6337823 |
KO, macroH2A1, Mock, Rep2 |
| GSM6337824 |
KO, macroH2A1, HSV-1 4 hpi, Rep2 |
| GSM6337825 |
KO, macroH2A1, HSV-1 8 hpi, Rep2 |
| GSM6337826 |
KO, macroH2A1, HSV-1 12 hpi, Rep2 |
| GSM6337827 |
KO, macroH2A1, Mock, Rep3 |
| GSM6337828 |
KO, macroH2A1, HSV-1 4 hpi, Rep3 |
| GSM6337829 |
KO, macroH2A1, HSV-1 8 hpi, Rep3 |
| GSM6337830 |
KO, macroH2A1, HSV-1 12 hpi, Rep3 |
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| This SubSeries is part of SuperSeries: |
| GSE209820 |
HSV-1 exploits host heterochromatin for nuclear egress |
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| Relations |
| BioProject |
PRJNA858438 |
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