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Inhibiting key protein halts herpes lytic cycle

Epigenetic controls like histone modification and chromatin remodeling play important regulatory roles in all cellular processes requiring access to the genome. So when a herpes simplex virus or varicella-zoster virus infects a human cell, one of the first things it does is attack the cell’s epigenetic modifications so it can gain access to the chromosome. Once these epigenetic controls are down, the lytic process can begin. In mBio this week, scientists from NIAID and elsewhere found a way to suppress the herpes virus’ ability to alter these epigenetic controls.

An important part of the lytic replication cycle, viral protein LSD1 does the heavy lifting in attacking a cell’s epigenetic modifications. Liang et al. identified a novel set of LSD1 inhibitors using in vitro assays, and in head-to-head testing with LSD1, one specific inhibitor, OG-L002, proved to be particularly effective. In cell culture, OG-L002 inhibited the expression of viral genes necessary for initiating the lytic cycle, and it suppressed lytic infection in a mouse model. The authors say this highlights the potential for drugs that inhibit a virus’ ability to modify chromatin for treating or even preventing viral diseases like herpes, chicken pox, and shingles.

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