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Histone Deacetylase Inhibitors Reduce the Number of Herpes Simplex Virus-1 Genomes Initiating Expression in Individual Cells
- Source :
- Frontiers in Microbiology, Vol 7 (2016), Frontiers in Microbiology
- Publication Year :
- 2016
- Publisher :
- Frontiers Media S.A., 2016.
-
Abstract
- Although many viral particles can enter a single cell, the number of viral genomes per cell that establish infection is limited. However, mechanisms underlying this restriction were not explored in depth. For herpesviruses, one of the possible mechanisms suggested is chromatinization and silencing of the incoming genomes. To test this hypothesis, we followed infection with three herpes simplex virus 1 (HSV-1) fluorescence-expressing recombinants in the presence or absence of histone deacetylases inhibitors (HDACi’s). Unexpectedly, a lower number of viral genomes initiated expression in the presence of these inhibitors. This phenomenon was observed using several HDACi: Trichostatin A (TSA), Suberohydroxamic Acid (SBX), Valporic Acid (VPA) and Suberoylanilide Hydoxamic Acid (SAHA). We found that HDACi presence did not change the progeny outcome from the infected cells but did alter the kinetic of the infection. Different cell types (HFF, Vero and U2OS), which vary in their capability to activate intrinsic and innate immunity, show a cell specific basal average number of viral genomes establishing infection. Importantly, in all cell types, treatment with TSA reduced the number of viral genomes. ND10 nuclear bodies are known to interact with the incoming herpes genomes and repress viral replication. The viral immediate early protein, ICP0, is known to disassemble the ND10 bodies and to induce degradation of some of the host proteins in these domains. HDACi treated cells expressed higher levels of some of the host ND10 proteins (PML and ATRX), which may down regulate the number of viral genomes initiating expression per cell. Corroborating this hypothesis, infection with three HSV-1 recombinants carrying a deletion in the gene coding for ICP0, show a reduction in the number of genomes being expressed in U2OS cells. We suggest that alterations in the levels of host proteins involved in intrinsic antiviral defense may result in differences in the number of genomes that initiate expression.
- Subjects :
- 0301 basic medicine
Microbiology (medical)
Intrinsic immunity
viruses
Histone deacetylase inhibitors
lcsh:QR1-502
Biology
ICP0 deletion
histone deacetylase inhibitors
medicine.disease_cause
Microbiology
lcsh:Microbiology
Immediate early protein
03 medical and health sciences
Viral entry
medicine
Gene silencing
virus host interactions
Original Research
030304 developmental biology
0303 health sciences
Innate immune system
030102 biochemistry & molecular biology
herpes simplex virus-1
030302 biochemistry & molecular biology
intrinsic immunity
Virology
Cell biology
3. Good health
030104 developmental biology
Herpes simplex virus
Trichostatin A
Histone
Viral replication
biology.protein
gene expression
Histone deacetylase
medicine.drug
Subjects
Details
- Language :
- English
- ISSN :
- 1664302X
- Volume :
- 7
- Database :
- OpenAIRE
- Journal :
- Frontiers in Microbiology
- Accession number :
- edsair.doi.dedup.....be94edc56474ed7ff9c2fc3333c8633a
- Full Text :
- https://doi.org/10.3389/fmicb.2016.01970