The vaccinia virus K7 protein promotes histone methylation associated with heterochromatin formation

Abstract

It has been well established that many vaccinia virus proteins suppress host antiviral pathways by targeting the transcription of antiviral proteins, thus evading the host innate immune system. However, whether viral proteins have an effect on the host’s overall cellular transcription is less understood. In this study we investigated the regulation of heterochromatin during vaccinia virus infection. Heterochromatin is a highly condensed form of chromatin that is less transcriptionally active and characterized by methylation of histone proteins. We examined the change in methylation of two histone proteins, H3 and H4, which are major markers of heterochromatin, during the course of viral infection. Using immunofluorescence microscopy and flow cytometry we were able to track the overall change in the methylated levels of H3K9 and H4K20. Our results suggest that there is significant increase in methylation of H3K9 and H4K20 during Orthopoxviruses infection compared to mock-infected cells. However, this effect was not seen when we infected cells with Leporipoxviruses. We further screened several vaccinia virus single and multi-gene deletion mutant and identified the vaccinia virus gene K7R as a contributor to the increase in cellular histone methylation during infection.

Detection of Nuclear Protein Profile Changes by Human Metapneumovirus M2-2 Protein Using Quantitative Differential Proteomics

“…As shown in Figure 5 D, the nuclear abundance of H4A was significantly increased by WT infection, and the mutations in M2-2 motifs resulted in increased H4A expression. Many viruses, including human cytomegalovirus, vaccinia virus, and herpes simplex virus regulate H3 protein expression or modify H3 methylation to change viral latency or replication [ 53 , 55 , 56 ]. Therefore, in this study, we selected H3 as a target to validate the effect of motifs on the summarized histone protein expression.…”

A poxvirus pseudokinase represses viral DNA replication via a pathway antagonized by its paralog kinase

“…We can only speculate as to the function of B12 in the nucleus at this time. Other poxviral proteins including C4 [70], C6 [71], C16 [72], B14 [73], K7 [74], N2 [75], F16 [76], and E3 [77] can be detected in the nucleus and have been found to impact innate immune signaling in most cases. However, there is no precedent to date for a nuclear poxviral protein affecting viral DNA replication.…”

Vaccinia virus-mediated cancer immunotherapy: cancer vaccines and oncolytics

“…Deletion of the gene led to a virus that is less pathogenic due to muted innate immune responses, yet still elicits protective immunity[39]K3LThe dsRNA-activated protein kinase (PKR) is inhibited by this pseudosubstrate inhibitorK3L prevents phosphorylation of e1F2α[189, 190]K7RPromotes histone methylation associated with heterochromatin associationK7R is a virulence gene; it inhibits the NF-κB pathway and thus the migration of neutrophil cells. It affects the acute immune response[37, 38, 191, 192]M1LAssociates with apoptosomeThe current model is that M1L associates with and allows the formation of the apoptosome, but prevents apoptotic functions of the apoptosome[193]N1LInhibits NF-κBN1L is a Bcl-2-like anti-apoptotic protein. It inhibits the NK cell response[194]Due to the limitation of the number of references that can be cited for this journal, not all relevant papers can be listed…”