PQBP1 Is a Proximal Sensor of the cGAS-Dependent Innate Response to HIV-1.
Cell
; 161(6): 1293-1305, 2015 Jun 04.
Article
em En
| MEDLINE
| ID: mdl-26046437
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Proteínas Nucleares
/
Proteínas de Transporte
/
HIV-1
/
Imunidade Inata
/
Nucleotidiltransferases
Limite:
Humans
Idioma:
En
Ano de publicação:
2015
Tipo de documento:
Article