连体细菌通过托代谢物托来抑制病毒感染
bioRxiv : the preprint server for biology
|April 25, 2024
概括
某些肠道细菌,如Clostridium immunis,可以通过代谢托来对抗HIV等病毒感染. 这条涉及酸受体 (AhR) 的途径提供了潜在的新型抗病毒疗法.
科学领域:
- 微生物学 微生物学
- 免疫学 免疫学 免疫学
- 病毒学 病毒学
背景情况:
- 连体细菌显著影响病毒感染结果,但机制尚不清楚.
- 了解特定的细菌及其在病毒抵抗中的作用对于开发新疗法至关重要.
研究的目的:
- 识别特定的开始性细菌及其赋予对病毒感染耐药性的机制.
- 调查酸催化和酸受体 (AhR) 途径在细菌抗病毒活性中的作用.
主要方法:
- 对一群被人类免疫缺陷病毒 (SHIV) 挑战的非人类灵长类动物进行生物信息分析.
- 在体外和体外实验中使用细菌分离物及其突变物来评估HIV复制抑制的实验.
- 来自艾滋病毒风险人群的人类便样本的元基因组分析.
主要成果:
- 乳酸菌 (Lactobacillus gasseri) 和Lachnospiraceae家族的细菌与对SHIV感染的抗性增强有关.
- 克洛斯特里免疫和鲁米诺科克斯 (Ruminococcus gnavus) 抑制了艾滋病毒的复制;这需要芳香氨基酸氨基转移酶 (ArAT) 基因.
- 由ArAT产生的代谢物3 - - 氨基酸 (ILA) 通过激活酸碳水化合物受体 (AhR) 来抑制HIV.
- 此外,C. immunis还通过一种依赖于ArAT的机制抑制了人类细胞巨血病毒 (HCMV).
- 细菌ArAT基因的便丰度较低与人类感染HIV相关.
结论:
- 连体细菌,特别是拉克诺斯皮拉属细菌,可以通过托分解抑制病毒复制.
- ArAT-ILA-AhR通路代表了一种新的微生物驱动的抗病毒防御机制.
- 这一途径在不同的病毒 (HIV,HCMV) 中得到保护,并转化为人类群体.
- 针对这种途径有望开发广泛的抗病毒疗法.
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