Frontiers in Cellular and Infection Microbiology (Jan 2023)

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

  • Carmen W.E. Embregts,
  • Annelieke S. Wentzel,
  • Alexander T. den Dekker,
  • Wilfred F.J. van IJcken,
  • Ralph Stadhouders,
  • Ralph Stadhouders,
  • Corine H. GeurtsvanKessel

DOI
https://doi.org/10.3389/fcimb.2023.1013842
Journal volume & issue
Vol. 13

Abstract

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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.

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