2. Academic Validation
  3. PQBP1 Is a Proximal Sensor of the cGAS-Dependent Innate Response to HIV-1

PQBP1 Is a Proximal Sensor of the cGAS-Dependent Innate Response to HIV-1

  • Cell. 2015 Jun 4;161(6):1293-1305. doi: 10.1016/j.cell.2015.04.050.
Sunnie M Yoh 1,  Monika Schneider 1,  Janna Seifried # 2,  Stephen Soonthornvacharin # 1,  Rana E Akleh 1,  Kevin C Olivieri 1,  Paul D De Jesus 1,  Chunhai Ruan 3,  Elisa de Castro 4,  Pedro A Ruiz 1,  David Germanaud 5,  Vincent des Portes 6,  Adolfo García-Sastre 4 7,  Renate König 2 1 8,  Sumit K Chanda 1
Affiliations

Affiliations

  • 1 Infectious and Inflammatory Disease Center, Sanford-Burnham Medical Research Institute, 10901 N. Torrey Pines Rd., La Jolla, CA 92116.
  • 2 Paul-Ehrlich-Institut, Paul-Ehrlich-Str. 51-59, D-63225 Langen, Germany.
  • 3 Department of Chemistry, University of Michigan, 930 N. University, Ann Arbor, MI 48109.
  • 4 Department of Microbiology, and Global Health and Emerging Pathogens Institute, Icahn School of Medicine at Mount Sinai, 1468 Madison Ave., New York, NY 10029.
  • 5 APHP, Hôpital Robert Debré, DHU PROTECT, Service de Neurologie Pédiatrique et Pathologie Métabolique, F-75019 Paris 2. Sorbonne Paris Cité, Université Paris Diderot, F-75010.
  • 6 National Reference Center for Fragile X and Other XLID, Biobank NeuroBioTec, Hospices Civils de Lyon, Université de Lyon and CNRS UMR 5304 (L2C2), Bron, France.
  • 7 Department of Medicine, Division of Infectious Diseases, Icahn School of Medicine at Mount Sinai, 1468 Madison Ave., New York, NY 10029.
  • 8 German Center for Infection Research (DZIF), Langen, Germany.
  • # Contributed equally.
PMID: 26046437 DOI: 10.1016/j.cell.2015.04.050
Abstract

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 Renpenning syndrome patients, who harbor mutations in the PQBP1 locus, possess a severely attenuated innate immune response to HIV-1 challenge, underscoring the role of PQBP1 as a proximal innate sensor of a HIV-1 Infection.

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