Work

In vitro demonstration of a potential role for STING agonist in HIV cure

Year: 2019

Type: article

Abstract: 1-58 45 we examined the host gene RNA landscape at the integration site.Fourth, to examine which cellular pathways mediates HIV-1 suppression, we performed transcriptome analysis and differential gene expression analysis in HIV-1-GFP reporter cell line models and in CD4 + T cells from HIV-1-infected individuals.Fifth, to examine the effect of HIV-1 suppressing agents on transcriptional landscape, we examined the intron retention landscape using IRFinder.Finally, to examine the impact of HIV-1-suppressing agents on the proliferation of HIV-1-infected cells, we examined the effect of HIV-1-suppressing agents on clonal expansion dynamics of HIV-1-infected CD4 + T cells by measuring the frequency of cells harboring inducible HIV-1 upon ex vivo CD3/CD28-induced proliferation with and without HIV-1 suppressing agents.Results: We identify a JAK1 inhibitor, filgotinib, which suppresses HIV-1 RNA splicing, HIV-1-driven aberrant host gene transcription through modulation of RNA splicing machinery.We found that filgotinib suppresses the clonal expansion of HIV-1-infected cells upon CD3/CD28-induced proliferation.Conclusions: We identified the mechanism of filgotinib-induced suppression of HIV-1-induced aberrant host gene transcription.We found that filgotinib suppresses proliferation of HIV-1-infected cells ex vivo.HIV-1 suppressing agents serve as a new class of therapeutic agents which disrupt clonal expansion of HIV-1-infected cells.PP 5.7.14

Source: Journal of Virus Eradication

DOI: 10.1016/s2055-6640(20)30194-1