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哺乳动物ZAP和KHNYN独立地限制了CpG丰富的禽类病毒

Jordan T Becker^1,2,3, Clayton K Mickelson¹, Lauren M Pross¹

¹Department of Microbiology and Immunology, University of Minnesota - Twin Cities, Minneapolis, MN, USA, 55455.

bioRxiv : the preprint server for biology

|January 7, 2025

概括

哺乳动物指抗病毒蛋白 (ZAP) 和其辅因子KHNYN通过准CpG丰富的RNA来限制病毒. 鸟类物种缺乏KHNYN,这可能使病毒能够逃避这种抗病毒防御.

科学领域:

病毒学病毒学
免疫学免疫学免疫学
遗传学是一个遗传学.

背景情况:

动物传播病毒,如流感A型病毒 (IAV),对全球健康构成重大风险,需要了解跨物种传播.
虽然已知前病毒性因素,但抑制动物性病毒感染的抗病毒机制仍然不太了解.
与鸟类IAV相比,在人类IAV中观察到CpG二核酸耗尽.

研究的目的:

调查指抗病毒蛋白 (ZAP) 和其辅因子KHNYN在限制动物性病毒感染中的作用.
探索鸟类和哺乳动物物种之间的ZAP-KHNYN抗病毒途径的进化差异.
为了确定KHNYN是否作为真诚的限制因素.

主要方法:

在禽流感A病毒 (IAV) 和人类流感A病毒 (IAV) 中对CpG二核酸含量的比较分析.
研究人类ZAP和KHNYN与CpG丰富的病毒RNA的相互作用.
使用ZAP和KHNYN在鸟类 () 和哺乳动物 (人类) 细胞系统中的功能测试,包括基因淘汰和过度表达.
测试哺乳动物ZAP-L和KHNYN对鸟类逆转录病毒 (ROSV) 和白 KHNYN对各种病毒的限制活性.

主要成果:

人类ZAP选择性地耗尽CpG丰富的病毒RNA,依赖于其辅因子KHNYN.
禽类缺乏KHNYN,而肉ZAP并没有限制IAV或CpG丰富的IAV.
人类ZAP或KHNYN在细胞或人体细胞中独立地限制了CpG丰富的IAV.
哺乳动物ZAP-L和KHNYN限制了ROSV,白 KHNYN显示出广泛的抗病毒活性.
KHNYN 显示了细胞自主活动,这表明它是一个真正的限制因子.

结论:

哺乳动物KHNYN作为真正的限制因子,具有针对各种病毒的细胞自主活性.
鸟类中 KHNYN 的缺失可能使病毒能够逃避哺乳动物的 ZAP-KHNYN 抗病毒防御.
像KHNYN这样的蛋白质因子的进化变化可能对病毒适应新宿主至关重要,可能涉及CpG偏差突变.

关键词:

生物科学生物科学这就是 KHNYNNN.微生物学微生物学罗斯肉瘤病毒的病毒.这就是ZAP ZAP.主体-病原体相互作用甲型流感病毒是流感的一种病毒.

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