IRF7 expression correlates with HIV latency reversal upon specific blockade of immune activation.

Autor:	Ezeonwumelu IJ; IrsiCaixa AIDS Research Institute - IrsiCaixa and Health Research Institute Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain., García-Vidal E; IrsiCaixa AIDS Research Institute - IrsiCaixa and Health Research Institute Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain., Felip E; IrsiCaixa AIDS Research Institute - IrsiCaixa and Health Research Institute Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.; Medical Oncology Department, Catalan Institute of Oncology (ICO)-Badalona, B-ARGO (Badalona Applied Research Group in Oncology) and IGTP (Health Research Institute Germans Trias i Pujol), Universitat Autònoma de Barcelona, Badalona, Spain., Puertas MC; IrsiCaixa AIDS Research Institute - IrsiCaixa and Health Research Institute Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.; Consorcio Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain., Oriol-Tordera B; IrsiCaixa AIDS Research Institute - IrsiCaixa and Health Research Institute Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain., Gutiérrez-Chamorro L; IrsiCaixa AIDS Research Institute - IrsiCaixa and Health Research Institute Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain., Gohr A; Scientific Computing Facility, Max Planck Institute of Molecular Cell Biology and Genetics, Dresden, Germany., Ruiz-Riol M; IrsiCaixa AIDS Research Institute - IrsiCaixa and Health Research Institute Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.; Consorcio Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain., Massanella M; IrsiCaixa AIDS Research Institute - IrsiCaixa and Health Research Institute Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.; Consorcio Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain., Clotet B; IrsiCaixa AIDS Research Institute - IrsiCaixa and Health Research Institute Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.; Consorcio Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.; Centre for Health and Social Care Research (CESS), Faculty of Medicine, University of Vic - Central University of Catalonia (UVic - UCC), Vic, Spain., Martinez-Picado J; IrsiCaixa AIDS Research Institute - IrsiCaixa and Health Research Institute Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.; Consorcio Centro de Investigación Biomédica en Red de Enfermedades Infecciosas (CIBERINFEC), Instituto de Salud Carlos III, Madrid, Spain.; Centre for Health and Social Care Research (CESS), Faculty of Medicine, University of Vic - Central University of Catalonia (UVic - UCC), Vic, Spain.; Catalan Institution for Research and Advanced Studies (ICREA), Barcelona, Spain., Badia R; IrsiCaixa AIDS Research Institute - IrsiCaixa and Health Research Institute Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain., Riveira-Muñoz E; IrsiCaixa AIDS Research Institute - IrsiCaixa and Health Research Institute Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain., Ballana E; IrsiCaixa AIDS Research Institute - IrsiCaixa and Health Research Institute Germans Trias i Pujol (IGTP), Hospital Germans Trias i Pujol, Universitat Autònoma de Barcelona, Badalona, Spain.
Jazyk:	angličtina
Zdroj:	Frontiers in immunology [Front Immunol] 2022 Sep 05; Vol. 13, pp. 1001068. Date of Electronic Publication: 2022 Sep 05 (Print Publication: 2022).
DOI:	10.3389/fimmu.2022.1001068
Abstrakt:	The persistence of latent HIV reservoirs allows for viral rebound upon antiretroviral therapy interruption, hindering effective HIV-1 cure. Emerging evidence suggests that modulation of innate immune stimulation could impact viral latency and contribute to the clearing of HIV reservoir. Here, the latency reactivation capacity of a subclass of selective JAK2 inhibitors was characterized as a potential novel therapeutic strategy for HIV-1 cure. Notably, JAK2 inhibitors reversed HIV-1 latency in non-clonal lymphoid and myeloid in vitro models of HIV-1 latency and also ex vivo in CD4+ T cells from ART+ PWH, albeit its function was not dependent on JAK2 expression. Immunophenotypic characterization and whole transcriptomic profiling supported reactivation data, showing common gene expression signatures between latency reactivating agents (LRA; JAK2i fedratinib and PMA) in contrast to other JAK inhibitors, but with significantly fewer affected gene sets in the pathway analysis. In depth evaluation of differentially expressed genes, identified a significant upregulation of IRF7 expression despite the blockade of the JAK-STAT pathway and downregulation of proinflammatory cytokines and chemokines. Moreover, IRF7 expression levels positively correlated with HIV latency reactivation capacity of JAK2 inhibitors and also other common LRAs. Collectively, these results represent a promising step towards HIV eradication by demonstrating the potential of innate immune modulation for reducing the viral reservoir through a novel pathway driven by IRF7. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Ezeonwumelu, García-Vidal, Felip, Puertas, Oriol-Tordera, Gutiérrez-Chamorro, Gohr, Ruiz-Riol, Massanella, Clotet, Martinez-Picado, Badia, Riveira-Muñoz and Ballana.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu