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10.3389/fimmu.2020.567348 http://scihub22266oqcxt.onion/10.3389/fimmu.2020.567348 33154747!7591719!33154747     free     free     free Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 233.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       Front+Immunol 2020 ; 11 (ä): 567348 Nephropedia Template TP {{tp|p=33154747|t=2020. Polymorphisms in STING Affect Human Innate Immune Responses to Poxviruses |pdf=|usr=}}{{33154747}} gab.com Text Polymorphisms in STING Affect Human Innate Immune Responses to Poxviruses JO: Front Immunol http://www.kidney.de/pget.php?&tw=1&pmid=33154747 #FOAvip We conducted a large genome-wide association study (GWAS) of the immune responses to primary smallpox vaccination in a combined cohort of 1,653 subjects. We did not observe any polymorphisms associated with standard vaccine response outcomes (e.g., neutralizing antibody, T cell ELISPOT response, or T cell cytokine production); however, we did identify a cluster of SNPs on chromosome 5 (5q31.2) that were significantly associated (p-value: 1.3 x 10(-12) - 1.5x10(-36)) with IFNalpha response to in vitro poxvirus stimulation. Examination of these SNPs led to the functional testing of rs1131769, a non-synonymous SNP in TMEM173 causing an Arg-to-His change at position 232 in the STING protein-a major regulator of innate immune responses to viral infections. Our findings demonstrate differences in the ability of the two STING variants to phosphorylate the downstream intermediates TBK1 and IRF3 in response to multiple STING ligands. Further downstream in the STING pathway, we observed significantly reduced expression of type I IFNs (including IFNalpha) and IFN-response genes in cells carrying the H232 variant. Subsequent molecular modeling of both alleles predicted altered ligand binding characteristics between the two variants, providing a potential mechanism underlying differences in inter-individual responses to poxvirus infection. Our data indicate that possession of the H232 variant may impair STING-mediated innate immunity to poxviruses. These results clarify prior studies evaluating functional effects of genetic variants in TMEM173 and provide novel data regarding genetic control of poxvirus immunity. Twit Text FOAVip Polymorphisms in STING Affect Human Innate Immune Responses to Poxviruses ????Front Immunol http://www.kidney.de/pget.php?&tw=1&pmid=33154747 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=33154747 #FOAvip English Wikipedia <ref>{{Cite pmid|33154747}}</ref> Polymorphisms in STING Affect Human Innate Immune Responses to Poxviruses #MMPMID33154747 Kennedy RB; Haralambieva IH; Ovsyannikova IG; Voigt EA; Larrabee BR; Schaid DJ; Zimmermann MT; Oberg AL; Poland GA Front Immunol 2020[]; 11 (ä): 567348 PMID33154747show ga We conducted a large genome-wide association study (GWAS) of the immune responses to primary smallpox vaccination in a combined cohort of 1,653 subjects. We did not observe any polymorphisms associated with standard vaccine response outcomes (e.g., neutralizing antibody, T cell ELISPOT response, or T cell cytokine production); however, we did identify a cluster of SNPs on chromosome 5 (5q31.2) that were significantly associated (p-value: 1.3 x 10(-12) - 1.5x10(-36)) with IFNalpha response to in vitro poxvirus stimulation. Examination of these SNPs led to the functional testing of rs1131769, a non-synonymous SNP in TMEM173 causing an Arg-to-His change at position 232 in the STING protein-a major regulator of innate immune responses to viral infections. Our findings demonstrate differences in the ability of the two STING variants to phosphorylate the downstream intermediates TBK1 and IRF3 in response to multiple STING ligands. Further downstream in the STING pathway, we observed significantly reduced expression of type I IFNs (including IFNalpha) and IFN-response genes in cells carrying the H232 variant. Subsequent molecular modeling of both alleles predicted altered ligand binding characteristics between the two variants, providing a potential mechanism underlying differences in inter-individual responses to poxvirus infection. Our data indicate that possession of the H232 variant may impair STING-mediated innate immunity to poxviruses. These results clarify prior studies evaluating functional effects of genetic variants in TMEM173 and provide novel data regarding genetic control of poxvirus immunity. |*Immunity, Innate/genetics[MESH] |*Polymorphism, Single Nucleotide[MESH] |Alleles[MESH] |Disease Susceptibility[MESH] |Founder Effect[MESH] |Gene Expression[MESH] |Genome-Wide Association Study[MESH] |Genotype[MESH] |Host-Pathogen Interactions/*genetics/*immunology[MESH] |Humans[MESH] |Immunogenetic Phenomena[MESH] |Ligands[MESH] |Membrane Proteins/*genetics/metabolism[MESH] |Models, Biological[MESH] |Phosphorylation[MESH] |Poxviridae Infections/*genetics/*immunology/virology[MESH] |Poxviridae/*immunology[MESH] |Promoter Regions, Genetic[MESH] |Protein Binding[MESH] |Protein Conformation[MESH]Polymorphisms in STING Affect Human Innate Immune Responses to Poxviru(epmc).pdf DeepDyve Pubget Overpricing