Polymorphisms in STING Affect Human Innate Immune Responses to Poxviruses.

ABSTRACT: 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 IFNα 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 findin

SUBMITTER: Kennedy RB 

PROVIDER: S-EPMC7591719 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature