Rare variant <em>MX1</em> alleles increase human susceptibility to zoonotic H7N9 influenza virus

doi:10.1126/science.abg5953

GSTDTAP > 气候变化

DOI	10.1126/science.abg5953
	*Rare variant MX1* alleles increase human susceptibility to zoonotic H7N9 influenza virus**
	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
	2021-08-20
发表期刊	Science
出版年	2021
英文摘要	What conditions are required to nurture the seeds of a pandemic? The avian influenza virus H7N9 rarely spills over into humans, but when it does, mortality exceeds 30%, far in excess of that of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Chen et al. used whole-genome sequencing to investigate the contribution of rare mutations among poultry workers, who can be exposed to high levels of H7N9. Multiple defective single-nucleotide variants in the myxovirus resistance Mx1 locus were prevalent in H7N9 patients. In vitro infection experiments and influenza polymerase activity assays showed that 14 of the 17 MxA protein variants had no antiviral activity. Thus, when exposed to high virus loads, individuals with such genetic vulnerabilities may act as crucibles for transmission of virulent new influenza subtypes. Science , abg5953, this issue p. [918][1] 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. [1]: /lookup/doi/10.1126/science.abg5953
领域	气候变化 ; 资源环境
URL	查看原文
引用统计
文献类型	期刊论文
条目标识符	http://119.78.100.173/C666/handle/2XK7JSWQ/336035
专题	气候变化资源环境科学
推荐引用方式 GB/T 7714	Yongkun Chen,Laura Graf,Tao Chen,et al. Rare variant MX1 alleles increase human susceptibility to zoonotic H7N9 influenza virus[J]. Science,2021.
APA	Yongkun Chen.,Laura Graf.,Tao Chen.,Qijun Liao.,Tian Bai.,...&Yuelong Shu.(2021).Rare variant MX1 alleles increase human susceptibility to zoonotic H7N9 influenza virus.Science.
MLA	Yongkun Chen,et al."Rare variant MX1 alleles increase human susceptibility to zoonotic H7N9 influenza virus".Science (2021).