Poster abstracts
Poster number 47 submitted by Zhihua Qin
The HD domain of SAMHD1 is required for its suppression of interferon regulatory factor 7-mediated type I interferon induction
Zhihua Qin (Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University), Shuliang Chen (Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University), Corine St. Gelais (Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University), Sun Hee Kim (Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University), Serena Bonifati (Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University), Li Wu (Center for Retrovirus Research, Department of Veterinary Biosciences, The Ohio State University)
Abstract:
Homozygous mutations of the gene encoding sterile alpha motif and HD domain containing protein 1 (SAMHD1) can cause Aicardi-Goutiè€res syndrome characterized by the induction of type I interferon (IFN-I), indicating that SAMHD1 is a negative regulator of the innate immune responses. Our recent studies identified that SAMHD1 interacts with IRF7 and inhibits IRF7-mediated IFN-I induction, resulting in suppression of innate immune responses to HIV-1 or Sendai virus infection. However, the domain of SAMHD1 responsible for the IRF7 interaction and IFN-I suppression have not been identified. We hypothesize that SAMHD1 and IRF7 interaction is required for the suppression of IRF7-mediated IFN-I induction by SAMHD1. To map the site of SAMHD1-IRF7 interaction, we generated a series of truncated SAMHD1 mutants and tested their interactions with full-length IRF7 through co-immunoprecipitation (co-IP) in HEK293T cells. We found that mutants lacking the HD domain did not interact with IRF7, suggesting that HD domain of SAMHD1 is important for IRF7 interaction. We then determined the contribution of the HD domain to suppression of IRF7-mediated IFN-I induction using an IFN-sensitive response element (ISRE) reporter assay. Our data showed that the HD domain of SAMHD1 is necessary and sufficient for IRF7 interaction and suppression of IFN-I induction. Our ongoing work is to examine the exact aa within HD domain responsible for the interaction with IRF7 and the suppression of IRF7-mediated ISRE activation using additional SAMHD1 mutants through co-IP assay and dual luciferase assay. Overall, our findings reveal the domain of SAMHD1 contributing to IFN-I inhibition, which help define the mechanisms of SAMHD1 in suppressing the innate immunity.
Keywords: SAMHD1, type I interferon induction, IRF7