Identification and Characterization of a Loss-of-Function Human MPYS Variant
| Autor: | Ivana V. Yang, David A. Schwartz, Elizabeth J. Davidson, John C. Cambier, Lei Jin, Mark M. Wurfel, Liang-Guo Xu |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2011 |
| Předmět: |
musculoskeletal diseases
Male Immunology Molecular Sequence Data SNP Single-nucleotide polymorphism Immunogenetics Biology Polymorphism Single Nucleotide Article DNA vaccination Cohort Studies 03 medical and health sciences 0302 clinical medicine Interferon Genetics medicine Animals Humans Listeriosis Amino Acid Sequence skin and connective tissue diseases Gene Genetics (clinical) 030304 developmental biology 0303 health sciences MPYS/STING/MITA Intracellular parasite Haplotype RNA Membrane Proteins Interferon-beta Virology Listeria monocytogenes 3. Good health Pedigree HEK293 Cells 030220 oncology & carcinogenesis anti-viral signaling Female Sequence Alignment IFNβ medicine.drug |
| Zdroj: | Genes and immunity |
| ISSN: | 1476-5470 1466-4879 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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