中国国家病毒疾病控制和预防研究所舒跃龙研究团队发现MX1等位基因罕见变异增加人类对人畜共患 H7N9 流感病毒的易感性。相关论文于2021年8月20日发表在《科学》杂志上。

他们使用全基因组测序将禽类A 型禽流感病毒 (IAV)H7N9 患者与健康对照进行比较，并观察到H7N9 感染与 MX1 基因中罕见的杂合单核苷酸变异之间存在很强的关联。MX1 编码粘液病毒抗性蛋白 A (MxA)，这是一种干扰素诱导的抗病毒鸟苷三磷酸酶，已知可控制转基因小鼠的 IAV 感染。大多数 MxA 变体在转染的人类细胞系中失去了抑制禽类 IAV 的能力，包括 H7N9。

几乎所有非活性 MxA 变体对野生型 MxA 的抗病毒功能都产生显性负效应，表明杂合子携带者中存在 MxA 无效表型。他们的研究为基于 MX1 的抗病毒防御在控制人类人畜共患病 IAV 感染中的关键作用提供了遗传证据。

据悉，人畜共患 IAV感染很少见。尚未观察到这些 IAV 在人类之间的持续传播，这表明宿主基因的作用。

附：英文原文

Title: Rare variant MX1 alleles increase human susceptibility to zoonotic H7N9 influenza virus

Author: Yongkun Chen, Laura Graf, Tao Chen, Qijun Liao, Tian Bai, Philipp P. Petric, Wenfei Zhu, Lei Yang, Jie Dong, Jian Lu, Ying Chen, Juan Shen, Otto Haller, Peter Staeheli, Georg Kochs, Dayan Wang, Martin Schwemmle, Yuelong Shu

Issue&Volume: 2021/08/20

Abstract: Zoonotic avian influenza A virus (IAV) infections are rare. Sustained transmission of these IAVs between humans has not been observed, suggesting a role for host genes. We used whole-genome sequencing to compare avian IAV H7N9 patients with healthy controls and observed a strong association between H7N9 infection and rare, heterozygous single-nucleotide variants in the MX1 gene. MX1 codes for myxovirus resistance protein A (MxA), an interferon-induced antiviral guanosine triphosphatase known to control IAV infections in transgenic mice. Most of the MxA variants identified lost the ability to inhibit avian IAVs, including H7N9, in transfected human cell lines. Nearly all of the inactive MxA variants exerted a dominant-negative effect on the antiviral function of wild-type MxA, suggesting an MxA null phenotype in heterozygous carriers. Our study provides genetic evidence for a crucial role of the MX1-based antiviral defense in controlling zoonotic IAV infections in humans.

DOI: 10.1126/science.abg5953

Source: https://science.sciencemag.org/content/373/6557/918