Identification and characterization of a loss-of-function human MPYS variant

被引：97

作者：

Jin, L. ^{[1
]}

Xu, L-G ^{[1
]}

Yang, I. V. ^{[2
,3
]}

Davidson, E. J. ^{[2
,3
]}

Schwartz, D. A. ^{[1
,2
,3
]}

Wurfel, M. M. ^{[4
]}

Cambier, J. C. ^{[1
]}

机构：

[1] Univ Colorado Denver, Sch Med, Integrated Dept Immunol, Natl Jewish Hlth, Denver, CO 80206 USA

[2] Natl Jewish Hlth, Dept Med, Denver, CO USA

[3] Natl Jewish Hlth, Ctr Genes Environm & Hlth, Denver, CO USA

[4] Univ Washington, Div Pulm & Crit Care Med, Seattle, WA 98195 USA

来源：

GENES AND IMMUNITY | 2011年 / 12卷 / 04期

关键词：

SNP; IFN beta; anti-viral signaling; MPYS/STING/MITA; LISTERIA-MONOCYTOGENES; ADAPTER; MUTATIONS; ACTIVATION; RECEPTORS; DOMAIN;

D O I：

10.1038/gene.2010.75

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

MPYS, also known as STING and MITA, is an interferon (IFN)beta stimulator essential for host defense against RNA, DNA viruses and intracellular bacteria. MPYS also facilitates the adjuvant activity of DNA vaccines. Here, we report identification of a distinct human MPYS haplotype that contains three non-synonymous single nucleotide polymorphisms (SNPs), R71 (H) under bar -G230 (A) under bar -R293 (Q) under bar (thus, named the HAQ haplotype). We estimate, in two cohorts (1074 individuals), that similar to 3% of Americans are homozygous for this HAQ haplotype. HAQ MPYS exhibits a >90% loss in the ability to stimulate IFN beta production. Furthermore, fibroblasts and macrophage cells expressing HAQ are defective in Listeria monocytogenes infection-induced IFN beta production. Lastly, we find that the loss of IFN beta activity is due primarily to the R71H and R293Q SNPs in HAQ. We hypothesize that individuals carrying HAQ may exhibit heightened susceptibility to viral infection and respond poorly to DNA vaccines. Genes and Immunity (2011) 12, 263-269; doi:10.1038/gene.2010.75; published online 20 January 2011

引用

页码：263 / 269

页数：7

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