通过重塑actin细胞骨架和细胞膜蛋白质,PRRSV促进细菌感染
Xiao Liu1, Fang Lv2, Yanan Zhu2
1State Key Laboratory for Animal Disease Control and Prevention, College of Veterinary Medicine, Lanzhou University, Lanzhou Veterinary Research Institute, Chinese Academy of Agricultural Sciences, Lanzhou, Gansu, China.
mBio
|September 12, 2025
概括
猪生殖和呼吸系统综合征病毒 (PRRSV) 通过通过FLNA和ITGα5.5改变actin细胞骨架,增加对二次细菌感染的易感性. 准这些蛋白质减少了小鼠的细菌入侵和死亡率.
科学领域:
- 兽医病毒学 兽医病毒学
- 免疫学 免疫学 免疫学
- 微生物学 微生物学
背景情况:
- 二次性细菌感染在病毒性疾病控制中构成重大挑战,导致经济损失巨大.
- 猪生殖和呼吸系统综合征病毒 (PRRSV) 经常因二次细菌感染而复杂化,其机制在很大程度上尚未被探索.
- 现有的理解归因于PRRSV诱导的免疫抑制敏感性,忽视了细胞水平的变化.
研究的目的:
- 阐明PRRSV感染增强对二次细菌感染易感性的机制.
- 为了研究actin细胞骨调节和特定蛋白质在病毒诱导的细菌入侵中的作用.
- 评估针对已识别的宿主因子的治疗潜力.
主要方法:
- 在小猪和小鼠中的PRRSV感染模型.
- 在体外细菌共感染试验.
- 转录组分析以识别改变的宿主基因表达.
- 使用向FLNA和ITGα5.5的lentiviralshRNA进行了淘汰研究.
- 评估细菌负载,死亡率和行为素细胞骨重组.
主要成果:
- 在小猪中,PRRSV感染显著增加了Klebsiella pneumoniae和Streptococcus suis 2型的肺部细菌负载.
- PRRSV,H1N1和PCV2感染上调了Filamin A (FLNA) 和Integrin α5 (ITGα5) 的表达,促进了细菌入侵.
- 消除FLNA或ITGα5减少了体外和体内细菌的入侵,保护小鼠免受死亡.
结论:
- PRRSV感染通过FLNA上调调节诱导了actin细胞骨的重新排列,从而促进了细菌入侵.
- 通过对ITGα5进行上调,PRRSV增强了细菌的粘附性,这进一步促进了FLNA介导的细胞骨变化.
- 针对FLNA和ITGα5代表了对抗病毒诱导的二次细菌感染的潜在策略.
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