Research and Reports on Genetics

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Short Communication - Research and Reports on Genetics (2022) Volume 4, Issue 5

Inhibition of DNA virus replication in histone methyltransferase

Mariela Monti*

Department of Molecular Neuroscience, University of Science and Technology, China

*Corresponding Author:
Mariela Monti
Department of Molecular Neuroscience
University of Science and Technology
E-mail:[email protected]

Received: 31-Aug-2022, Manuscript No. AARRGS-22-77619;Editor assigned: 06-Sep-2022, PreQC No. AARRGS-22-77619(PQ); Reviewed: 20-Sep-2022, QC No. AARRGS-22-77619; Revised: 23-Sep-2022, Manuscript No. AARRGS-22-77619(R); Published: 28-Sep-2022, DOI:10.35841/aarrgs-4.5.125

Citation: Monti M. Inhibition of DNA virus replication in histone methyl transferase. J Res Rep Genet. 2022;4(5):125

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Several diseases, such as cancer and neurodegenerativediseases are associated with latent infection with DNAviruses. However eliminating latent DNA viruses remainsa challenge, and new antiviral strategies are essential fortreating the disease. Here we screen a pool of small chemicalmolecules and identify a histone ethyltransferase inhibitor asa potent inhibitor of several DNA viruses not only enhancesantiviral gene expression in THP-1 cells, but also suppressesviral DNA replication in several cGAS pathway-deficient celllines. We show that SETD8 promotes DNA virus replicationdependent on its enzymatic activity. Our results furthershowed that SETD8 is required for PCNA stability, a keyfactor in viral DNA replication. Viral infection stimulates theinteraction between SETD8 and PCNA, improving PCNAstability and viral DNA replication. Taken together, our studyreveals a novel mechanism regulating viral DNA replicationand provides potential strategies for treating DNA virusassociated diseases [1]

Initiates mismatch repair by detecting mismatches in newly replicated DNA. Specific interactions between and mismatches within the double-stranded DNA promote ADPATP exchange and conformational change to the sliding clamp. Here, we showed that Pseudomonas aeruginosa MutS associates with primed DNA replication intermediates. The predicted structure of this MutS-DNA complex revealed a novel DNA-binding site in which and appear to interact directly with her 3′-OH end of primed DNA. Mutation of these residues resulted in marked defects in interaction of MutS with primed DNA substrates. Strikingly, interaction of MutS with mismatches within primed DNA induced a tightening of protein structure and prevented the formation of ATP-bound slide clamps. Our results demonstrate novel DNA binding modes, conformational changes, and intermolecular signalling for MutS mismatch detection within primed DNA structures[2].

Viral infections are the cause of many diseases and are one of the greatest threats to human health worldwide. Compared to RNA viruses, DNA viruses infect large numbers of people worldwide and are much more difficult to purify due to their potential for infection. Innate immunity mediated by the cGAS pathway is believed to be the primary pathway for human cells to fight DNA viruses. Viral double-stranded DNA is recognized by cGAS, which synthesizes the second messenger cGAMP that activates signalling pathways. cGAMP then activates a key adapter protein it recruits and promotes phosphorylation of TANK-binding kinase 1 (TBK1) and subsequent phosphorylation of interferon regulatory factor 3. Phosphorylated IRF3 enters the nucleus and turns on the expression of type I interferon’s. Interferon then further activates the JAK/STAT pathway to express multiple antiviral genes and eliminate viruses interestingly, many cell types, especially cultured cancer cell lines, lack the cGAS pathway upon viral infection. It will be interesting to investigate whether other antiviral signalling pathways exist in these cells[3].

DNA viruses are typically much larger than RNA viruses and encode more proteins, which can lead to more complex cellular responses. Transcriptomic studies have shown that DNA virus infections often cause alterations in numerous host genes, suggesting that virus-host-cell interactions are highly complex. After infection, the DNA virus genome quickly enters the host cell nucleus, transcribes the viral genes, and undergoes rapid DNA replication. Viruses use a combination of viral and host protein machinery to navigate their life cycle. For example, several viral proteins such as ICP4 and ICP8 are enriched in the viral genome during HSV-1 DNA replication, along with cellular PCNA and topoisomerases [4].

Recent studies have shown that many epigenetic factors, such as histones, bind to the viral genome and play important rolesin viral gene transcription and DNA replication. Variousforms of histone modifications have also been detected inthe viral genome They appear in the viral genome rapidlyafter infection and change dynamically during the viral lifecycle. The formation of heterochromatin marks on the HSV1 genome has been reported to be important for orderedgenes Inhibition of the histone H3K4 demethylase LSD1results in heterochromatin repression of the HSV-1 genome,which subsequently affects viral infection epigenome studiesused high-throughput sequencing to map the location ofnucleosomes on the HSV-1 An epigenetic study of theHSV-1 genome showed that histone H3K9me3 decreasedand H3K27ac increased during the viral life cycle and thatC646, an inhibitor of H3K27ac, could suppress his HSV-1 incultured cells. Several histone modification landscapes on theKHSV genome have also been described in vitro and in vivo.It will be interesting to know whether other modified histonesare also present in the viral genome and regulate viral activity.In the current study, we performed a screen using a pool ofepigenetic factor inhibitors to identify potential epigeneticassociated small-molecule chemicals that suppress DNAviruses. We then found that UNC0379, an inhibitor of theH4K20 methyltransferase SETD8, could suppress severalDNA viruses. Further studies then show that SETD8 promotesDNA virus replication by stabilizing the host factor PCNAand promoting viral genome replication [5].


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