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

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TitlePQBP1 Is a Proximal Sensor of the cGAS-Dependent Innate Response to HIV-1.
Publication TypeJournal Article
Year of Publication2015
AuthorsYoh SM, Schneider M, Seifried J, Soonthornvacharin S, Akleh RE, Olivieri KC, De Jesus PD, Ruan C, de Castro E, Ruiz PA, Germanaud D, Portes Vdes, García-Sastre A, König R, Chanda SK
JournalCell
Volume161
Issue6
Pagination1293-305
Date Published2015 Jun 4
ISSN1097-4172
KeywordsBase Sequence, Carrier Proteins, Cell Line, Cerebral Palsy, DNA, Viral, HIV-1, Humans, Immunity, Innate, Mental Retardation, X-Linked, Molecular Sequence Data, Nuclear Proteins, Nucleotidyltransferases
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.

DOI10.1016/j.cell.2015.04.050
Alternate JournalCell
PubMed ID26046437
PubMed Central IDPMC4503237
Grant ListP01 AI090935 / AI / NIAID NIH HHS / United States
P01 AI090935 / AI / NIAID NIH HHS / United States
P01 CA177322 / CA / NCI NIH HHS / United States
P01 CA177322 / CA / NCI NIH HHS / United States
P50 GM085764 / GM / NIGMS NIH HHS / United States
R01 AI105184 / AI / NIAID NIH HHS / United States
R01 AI105184 / AI / NIAID NIH HHS / United States
U19 AI106754 / AI / NIAID NIH HHS / United States
U19 AI106754 / AI / NIAID NIH HHS / United States
U24 DK097153 / DK / NIDDK NIH HHS / United States