基因素陪伴者HIRA的染色体组装有助于人类乳头瘤病毒的复制
Ashley N Della Fera1, Dan Chen1, Alison A McBride1
1Laboratory of Viral Diseases, National Institute of Allergy and Infectious Diseases, 33 North Drive, MSC3209, National Institutes of Health, Bethesda, Maryland 20892, USA.
bioRxiv : the preprint server for biology
|September 29, 2025
概括
人类乳头瘤病毒 (HPV) 使用宿主细胞机器进行复制. 组织素伴侣HIRA和组织素H3.3被招募到HPV复制部位,促进病毒DNA放大和转录.
科学领域:
- 分子病毒学分子病毒学
- 表观遗传学 在表观遗传学中,表观遗传学是指表观遗传学.
- 染色体生物学 染色体生物学
背景情况:
- 人类乳头瘤病毒 (HPV) 具有圆形的双链DNA基因组.
- HPV DNA 存在于核体状态,其生命周期依赖宿主表观遗传修饰和染色质组合.
研究的目的:
- 为了研究基因组伴侣和特定基因组修饰在HPV生命周期中的作用.
- 为了确定HPVE1和E2蛋白在招募宿主因子中的充分性.
主要方法:
- 招募HIRA及其复杂HPV复制工厂的测定.
- 在HIRA下调后对HPVDNA放大和病毒转录的分析.
- 在HPV复制部位检测 histone H3.3 酸化.
主要成果:
- 在晚期阶段,HIRA及其相关复合物被招募到HPV复制工厂.
- 对于HIRA招募,HPV E1和E2蛋白质是足够的.
- HIRA下调减少了HPV31的DNA放大和病毒转录.
- 酸化组合素H3.3 (H3.3-S31ph) 在HPV复制部位富含.
结论:
- HIRA通过促进DNA放大和转录来促进HPV生命周期的后期阶段.
- 基因组H3.3沉积,特别是H3.3-S31ph,将DNA损伤反应与染色质原始化联系起来,以激活病毒基因.
- 这些发现表明,组素H3.3产生了为晚期HPV复制预先准备的病毒微染色体.
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