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BTN3A3逃避促进了A型流感病毒的动物感染潜力

Rute Maria Pinto^1,2, Siddharth Bakshi¹, Spyros Lytras¹

¹MRC-University of Glasgow Centre for Virus Research, Glasgow, UK.

|June 28, 2023

概括

人类布蒂罗菲林亚系3成员A3 (BTN3A3) 抑制禽流感A型病毒 (IAV),但不抑制人类IAV. 这一发现为鸟类感染病毒的感染潜力和疫情风险评估提供了新的见解.

科学领域:

病毒学
免疫学
遗传学

背景情况:

禽流感A型病毒 (IAV) 传播给人类,构成流行病的风险.
对于风险评估至关重要的是了解限制鸟类IAV传播的因素.
预测哪些鸟类IAV可以跨越物种障碍仍然是一个挑战.

研究的目的:

识别限制鸟类IAV在人类中的宿主因素.
调查人类丁素亚系3成员A3 (BTN3A3) 在限制鸟类IAV中的作用.
为了确定BTN3A3敏感性和逃避在禽类和人类的IAV的遗传基础.

主要方法:

鉴定人类BTN3A3作为禽类IAV的抑制剂.
对人类呼吸道BTN3A3表达的分析及其在灵长类动物中的进化起源.
针对早期病毒RNA复制的BTN3A3抗病毒机制的研究.
对BTN3A3敏感性/逃避性的遗传决定因素 (313和52在病毒核蛋白中的残留物) 的映射.

主要成果:

人类BTN3A3强烈抑制鸟类IAV,但人类IAV并非如此,其活性在灵长类动物中演变.
在病毒生命周期的早期发生BTN3A3限制,抑制鸟类IAVRNA复制.
病毒核蛋白残留313 (鸟类中的F/L与人类的Y/V) 确定BTN3A3的敏感性.
像H7和H9这样的鸟类IAV通过相邻的NP残留物52的替代而逃避BTN3A3.

结论:

人类BTN3A3作为对禽类IAV的限制因素.
由特定的病毒核蛋白残留物决定的BTN3A3敏感性/耐药性是鸟类IAV动物感染潜力的关键因素.
这为评估禽流感病毒带来的流行风险提供了一个新的参数.

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