Type I IFN signaling blockade by a PASylated antagonist during chronic SIV infection suppresses specific inflammatory pathways but does not alter T cell activation or virus replication.

PLoS Pathogens
Krystelle Nganou-MakamdopDaniel C Douek

Abstract

Chronic activation of the immune system in HIV infection is one of the strongest predictors of morbidity and mortality. As such, approaches that reduce immune activation have received considerable interest. Previously, we demonstrated that administration of a type I interferon receptor antagonist (IFN-1ant) during acute SIV infection of rhesus macaques results in increased virus replication and accelerated disease progression. Here, we administered a long half-life PASylated IFN-1ant to ART-treated and ART-naïve macaques during chronic SIV infection and measured expression of interferon stimulated genes (ISG) by RNA sequencing, plasma viremia, plasma cytokines, T cell activation and exhaustion as well as cell-associated virus in CD4 T cell subsets sorted from peripheral blood and lymph nodes. Our study shows that IFN-1ant administration in both ART-suppressed and ART-untreated chronically SIV-infected animals successfully results in reduction of IFN-I-mediated inflammation as defined by reduced expression of ISGs but had no effect on plasma levels of IL-1β, IL-1ra, IL-6 and IL-8. Unlike in acute SIV infection, we observed no significant increase in plasma viremia up to 25 weeks after IFN-1ant administration or up to 15 weeks af...Continue Reading

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Citations

Dec 27, 2018·Current Opinion in HIV and AIDS·Timothy N Hoang, Mirko Paiardini
Feb 15, 2019·Virologica Sinica·Krystelle Nganou-Makamdop, Daniel C Douek
Mar 15, 2019·Journal of Virology·Jessica Katy SkeltonMarcus Dorner
Jan 17, 2020·Journal of Virology·Jérémie PrévostJimmy D Dikeakos
Jul 22, 2020·Nature Neuroscience·Federico GiovannoniFrancisco J Quintana
Dec 31, 2020·International Journal of Molecular Sciences·Uli Binder, Arne Skerra
Mar 30, 2021·Frontiers in Pharmacology·Yunlian ZhouJie Zhu
Jun 30, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Stéphane IsnardAnne Hosmalin

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Methods Mentioned

BETA
RNA-seq
ELISA

Software Mentioned

GSEA
DESeq2

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