Scholarlink

<p>Herpes simplex virus-1 (HSV-1) establishes a latent infection in neurons, periodically reactivating to cause disease. Neuronal conditions, including immune signaling, during initial HSV-1 infection, impact later reactivation. Type I interferon (IFNα) exposure during initial infection results in promyelocytic leukemia nuclear-body (PML-NB) formation and subsequent restriction of reactivation, via mechanisms that were unknown. Here we find that PML-NB formation results in the recruitment of histone chaperones to the viral genome and increased enrichment of the repressive heterochromatin mark, histone H3 lysine 9 tri-methylation (H3K9me3), and its reader, ATRX (alpha-thalassemia/mental retardation, X-linked). ATRX is highly abundant in neurons and prevents reactivation from H3K9me3-bound latent genomes by remaining associated with viral chromatin. Therefore, we demonstrate how immune signaling during initial infection results in an epigenetic memory on HSV-1 genomes and identify ATRX as a neuronal restriction factor against HSV-1 reactivation, elucidating a new potential target for inhibiting HSV-1 reactivation and subsequent human disease.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Interferon dependent immune memory during HSV-1 neuronal latency via increased H3K9me3 and restriction by ATRX

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2025年12月1日

查看全文
  • Abigail L. Whitford,
  • Gaelle Auguste,
  • Alison K. Francois,
  • David J. Picketts,
  • Chris Boutell,
  • Clint L. Miller,
  • Sarah Dremel,
  • Anna. R. Cliffe

摘要

Herpes simplex virus-1 (HSV-1) establishes a latent infection in neurons, periodically reactivating to cause disease. Neuronal conditions, including immune signaling, during initial HSV-1 infection, impact later reactivation. Type I interferon (IFNα) exposure during initial infection results in promyelocytic leukemia nuclear-body (PML-NB) formation and subsequent restriction of reactivation, via mechanisms that were unknown. Here we find that PML-NB formation results in the recruitment of histone chaperones to the viral genome and increased enrichment of the repressive heterochromatin mark, histone H3 lysine 9 tri-methylation (H3K9me3), and its reader, ATRX (alpha-thalassemia/mental retardation, X-linked). ATRX is highly abundant in neurons and prevents reactivation from H3K9me3-bound latent genomes by remaining associated with viral chromatin. Therefore, we demonstrate how immune signaling during initial infection results in an epigenetic memory on HSV-1 genomes and identify ATRX as a neuronal restriction factor against HSV-1 reactivation, elucidating a new potential target for inhibiting HSV-1 reactivation and subsequent human disease.