biostudies-literatureYoh SMNIDDK NIH HHSNIDA NIH HHSNIAID NIH HHSNCI NIH HHSNIGMS NIH HHS1293-1305https://www.ebi.ac.uk/biostudies/studies/S-EPMC4503237biostudies-literatureUnknown161(6)Dendritic cells (DCs) play a critical role in the immune response to viral infection through the facilitation of cell-intrinsic antiviral activity and the activation of adaptive immunity. HIV-1 infection of DCs triggers an IRF3-dependent innate immune response, which requires the activity of cyclic GAMP synthase (cGAS). We report the results of a targeted RNAi screen utilizing primary human monocyte-derived DCs (MDDCs) to identify immune regulators that directly interface with HIV-1-encoded features to initiate this innate response. Polyglutamine binding protein 1 (PQBP1) emerged as a strong candidate through this analysis. We found that PQBP1 directly binds to reverse-transcribed HIV-1 DNA and interacts with cGAS to initiate an IRF3-dependent innate response. MDDCs derived from RenpenningCellPQBP1 Is a Proximal Sensor of the cGAS-Dependent Innate Response to HIV-1.PMC4503237U19 AI106754R01 DA033773U24 DK097153P50 GM085764P01 AI090935P01 CA177322P30 CA030199R01 AI105184Yoh SMdes Portes VGarcia-Sastre AKonig RSchneider MSeifried JDe Jesus PDChanda SKGermanaud DOlivieri KCRuan CRuiz PASoonthornvacharin Sde Castro EAkleh REfalsePQBP1 Is a Proximal Sensor of the cGAS-Dependent Innate Response to HIV-1.Dendritic cells (DCs) play a critical role in the immune response to viral infection through the facilitation of cell-intrinsic antiviral activity and the activation of adaptive immunity. HIV-1 infection of DCs triggers an IRF3-dependent innate immune response, which requires the activity of cyclic GAMP synthase (cGAS). We report the results of a targeted RNAi screen utilizing primary human monocyte-derived DCs (MDDCs) to identify immune regulators that directly interface with HIV-1-encoded features to initiate this innate response. Polyglutamine binding protein 1 (PQBP1) emerged as a strong candidate through this analysis. We found that PQBP1 directly binds to reverse-transcribed HIV-1 DNA and interacts with cGAS to initiate an IRF3-dependent innate response. MDDCs derived from Renpenning2015-01-01T00:00:00Z2015 Jun2025-04-19T07:18:30.119Z2019-03-27T01:55:10ZS-EPMC45032372604643710.1016/j.cell.2015.04.050