乌比基因特异蛋白酶1稳定PRRSV非结构蛋白Nsp1β,通过调节K48的乌比基因化,促进病毒复制
Yunyun Zhai1,2, Yongkun Du1,2, Hang Yuan3
1College of Veterinary Medicine, Henan Agricultural University, Zhengzhou, Henan, China.
Journal of virology
|February 20, 2024
概括
猪生殖和呼吸系统综合征病毒 (PRRSV) 劫持宿主泛素特异蛋白酶1 (USP1) 以稳定其NSP1β蛋白,增强病毒复制. 抑制USP1提供了针对PRRSV感染的新策略.
科学领域:
- 病毒学 病毒学
- 分子生物学分子生物学
- 免疫学 免疫学 免疫学
背景情况:
- 猪生殖和呼吸系统综合征病毒 (PRRSV) 在养猪业造成重大经济损失.
- 翻译后的修改,包括无处不在,对于PRRSV复制和持久性至关重要.
- 在PRRSV感染中,无素网络的作用在很大程度上仍未被探索.
研究的目的:
- 为了研究duebiquitinating酶在PRRSV感染中的作用.
- 为了确定PRRSV利用的宿主因子进行复制.
- 探索PRRSV控制的潜在治疗点.
主要方法:
- 对抗PRRSV的二基化酶抑制剂的查.
- 在体外测试以评估PRRSV复制.
- 同免疫沉检测蛋白质相互作用.
- 位点定向突变发生,以识别关键氨基酸残留物.
主要成果:
- 无素特异蛋白酶1 (USP1) 抑制剂ML323显著降低了PRRSV的复制in vitro.
- 发现USP1与PRRSV非结构蛋白1β (Nsp1β) 相互作用.
- USP1在K48处对Nsp1β进行二基化,增加其稳定性并促进病毒复制. USP1缺陷或突变在K45的NSP1β病毒复制受损.
结论:
- PRRSV招募宿主USP1,以使Nsp1β脱和稳定,从而促进病毒复制.
- USP1充当病毒宿主因子,使PRRSV能够逃避宿主免疫反应.
- 向USP1为控制PRRSV提供了一个新的治疗策略.
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