Abstract
During bovine herpesvirus 1 (BoHV-1) productive infection in cell cultures, partial of intranuclear viral DNA is present in nucleosomes, and viral protein VP22 associates with histones and decreases histone H4 acetylation, indicating the involvement of histone H4 acetylation in virus replication. In this study, we demonstrated that BoHV-1 infection at the late stage (at 24 h after infection) dramatically decreased histone H3 acetylation [at residues K9 (H3K9ac) and K18 (H3K18ac)], which was supported by the pronounced depletion of histone acetyltransferases (HATs) including CBP/P300 (CREB binding protein and p300), GCN5L2 (general control of amino acid synthesis yeast homolog like 2) and PCAF (P300/CBP-associated factor). The depletion of GCN5L2 promoted by virus infection was partially mediated by ubiquitin-proteasome pathway. Interestingly, the viral replication was enhanced by HAT (histone acetyltransferase) activator CTPB [N-(4-Chloro-3-trifluoromethylphenyl)-2-ethoxy-6-pentadecylbenzamide], and vice versa, inhibited by HAT inhibitor Anacardic acid (AA), suggesting that BoHV-1 may take advantage of histone acetylation for efficient replication. Taken together, we proposed that the HAT-dependent histone H3 acetylation plays an important role in BoHV-1 replication in MDBK (Madin-Darby bovine kidney) cells.
Highlights
Bovine herpesvirus 1 (BoHV-1) is an important pathogen that causes pneumonia, conjunctivitis, genital disorders, and abortions in cattle [1]
In view that the proteasome inhibitors of both MG132 and bortezomib could rescue the depletion depletion of H3K9ac attributed to virus infection, we investigated of H3K9ac attributed to virus infection, we investigated whether H3K9ac was ubiquitinated in the cells with or without infection by IP assay
For the first time we demonstrated that histone H3 acetylation (H3K9ac and H3K18ac) was significantly decreased during BoHV-1 infection in MDBK cells, and peaked at 24 h after infection (Figure 1), which suggested the involvement of histone
Summary
Bovine herpesvirus 1 (BoHV-1) is an important pathogen that causes pneumonia, conjunctivitis, genital disorders, and abortions in cattle [1]. [5,6], and lead to a life-threatening pneumonia known as bovine respiratory disease complex (BRDC), one of the costliest ailments in cattle feeding [7,8]. DNA is packaged into a protein-DNA complex called chromatin, with nucleosome as monomeric subunit containing a core of histone proteins Viruses 2018, 10, 525 transcriptionally repressed chromatin (heterochromatin) through diverse epigenetic modifications, such as by acetylation, methylation, ubiquitination, phosphorylation, and sumoylation [10,11,12,13]. The acetylation of certain lysine (K) residues in histones H3 and H4 is generally an indicator of transcriptionally active chromatin [14,15]
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