Rabies virus uniquely reprograms the transcriptome of human monocyte-derived macrophages

Carmen W.E. Embregts (Corresponding author), Annelieke S. Wentzel, Alexander T. den Dekker, Wilfred F.J. van IJcken, Ralph Stadhouders, Corine H. Geurts van Kessel

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Abstract

Macrophages are amongst the first immune cells that encounter rabies virus (RABV) at virus entry sites. Activation of macrophages is essential for the onset of a potent immune response, but insights into the effects of RABV on macrophage activation are scarce. In this study we performed high-throughput sequencing on RNA extracted from macrophages that were exposed to RABV for 48 hours, and compared their transcriptional profiles to that of non-polarized macrophages (M0), and macrophages polarized towards the canonical M1, M2a and M2c phenotypes. Our analysis revealed that RABV-stimulated macrophages show high expression of several M1, M2a and M2c signature genes. Apart from their partial resemblance to these phenotypes, unbiased clustering analysis revealed that RABV induces a unique and distinct polarization program. Closer examination revealed that RABV induced multiple pathways related to the interferon- and antiviral response, which were not induced under other classical polarization strategies. Surprisingly, our data show that RABV induces an activated rather than a fully suppressed macrophage phenotype, triggering virus-induced activation and polarization. This includes multiple genes with known antiviral (e.g. APOBEC3A, IFIT/OAS/TRIM genes), which may play a role in anti-RABV immunity.

Original languageEnglish
Article number1013842
Number of pages11
JournalFrontiers in Cellular and Infection Microbiology
Volume13
DOIs
Publication statusPublished - 31 Jan 2023

Funding

This work was funded through an Erasmus MC Fellowship 2019, project number 110581. CE is funded by a VENI Grant from the Netherlands Organization for Scientific Research (NWO-VENI 09150162010181).

FundersFunder number
Nederlandse Organisatie voor Wetenschappelijk OnderzoekNWO-VENI 09150162010181

    Keywords

    • Rabies Virus
    • Lyssavirus
    • Macrophage polarization
    • Innate immunity
    • Transcriptomics
    • RNA sequencing
    • innate immunity
    • transcriptomics
    • macrophage polarization
    • rabies virus (RABV)

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