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

Genes & Immunity volume 12, pages 263–269 (2011)Cite this article

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Abstract

MPYS, also known as STING and MITA, is an interferon (IFN)β 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), R71H-G230A-R293Q (thus, named the HAQ haplotype). We estimate, in two cohorts (1074 individuals), that ∼3% of Americans are homozygous for this HAQ haplotype. HAQ MPYS exhibits a >90% loss in the ability to stimulate IFNβ production. Furthermore, fibroblasts and macrophage cells expressing HAQ are defective in Listeria monocytogenes infection-induced IFNβ production. Lastly, we find that the loss of IFNβ 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.

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Acknowledgements

This work was supported by NIH 3R01AI062739-05S209 (JCC), 5R01AI062739-05 (JCC), HL089807-01 (MMW) and NIH U19 ES11375 (DAS and IVY) JCC is Ida and Cecil Green Professor of Immunology. We thank Dr Barber GN for providing STING−/− Femurs. For the human studies, we gratefully acknowledge all participants.

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Authors and Affiliations

  1. Integrated Department of Immunology, University of Colorado Denver School of Medicine and National Jewish Health, Denver, CO, USA

    L Jin, L-g Xu, D A Schwartz & J C Cambier

  2. Department of Medicine and Center for Genes, Environment, and Health, National Jewish Health, Denver, CO, USA

    I V Yang, E J Davidson & D A Schwartz

  3. Division of Pulmonary and Critical Care Medicine, University of Washington, Seattle, WA, USA

    M M Wurfel

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  1. L Jin
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  2. L-g Xu
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  7. J C Cambier
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Correspondence to J C Cambier.

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Jin, L., Xu, Lg., Yang, I. et al. Identification and characterization of a loss-of-function human MPYS variant. Genes Immun 12, 263–269 (2011). https://doi.org/10.1038/gene.2010.75

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