Histone modifications control the lytic gene expression of herpes simplex virus 1 (HSV-1).The heterochromatin mark, trimethylation of histone H3 on lysine (K) 9 (H3K9me3), is detected on HSV-1 genomes at early phases of infection to repress viral gene transcription.However, the components and click here mechanisms involved in the process are mostly unknown.Integrin-linked kinase (ILK) is activated by PI3K to phosphorylate Akt and promote several RNA virus infections.Akt has been shown to enhance HSV-1 infection, suggesting a pro-viral role of ILK in HSV-1 infection that has not been addressed before.
Here, we reveal that ILK enhances HSV-1 replication in an Akt-independent manner.ILK reduces the accumulation of H3K9me3 on viral promoters and replication compartments.Notably, ILK reduces H3K9me3 in a manner independent of ICP0.Instead, we show an increased binding of H3K9 methyltransferase SUV39H1 and corepressor TRIM28 on viral promoters in ILK knockdown cells.Knocking down SUV39H1 or TRIM28 increases HSV-1 lytic gene transcription in ILK knockdown cells.
These results show that ILK antagonizes SVU39H1- and TRIM28-mediated repression on lytic gene transcription.We further superdry baseball top demonstrate that ILK knockdown reduces TRIM28 phosphorylation on serine 473 and 824 in HSV-1-infected cells, suggesting that ILK facilitates TRIM28 phosphorylation to abrogate its inhibition on lytic gene transcription.OSU-T315, an ILK inhibitor, suppresses HSV-1 replication in cells and mice.In conclusion, we demonstrate that ILK decreases H3K9me3 on HSV-1 DNA by reducing SUV39H1 and TRIM28 binding.Moreover, our results suggest that targeting ILK could be a broad-spectrum antiviral strategy for DNA and RNA virus infections, especially for DNA viruses controlled by histone modifications.