In Vitro Characterization of the Innate Immune Pathways Engaged by Live and Inactivated Tick-Borne Encephalitis Virus

Aurora Signorazzi, Jeroen L. A. Pennings, Marilena P. Etna, Malou Noya, Eliana M. Coccia, Anke Huckriede*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

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Abstract

Tick-borne encephalitis virus (TBEV) infection can lead to inflammation of the central nervous system. The disease can be effectively prevented by whole inactivated virus vaccines. Here, we investigated the innate immune profile induced in vitro by the antigen component of the vaccines, inactivated TBEV (I-TBEV), to gain insights into the mechanism of action of the TBE vaccine as compared to the live virus. To this end, we exposed human peripheral blood mononuclear cells (PBMCs) to inactivated and live TBEV and assessed cellular responses by RNA sequencing. Both inactivated and live TBEV significantly induced an interferon-dominated gene signature and an increased RIG-I-like receptor (RLR) expression. Using pathway-specific inhibitors, we assessed the involvement of pattern recognition receptors in the sensing of inactivated or live TBEV. Only RLR pathway inhibition significantly suppressed the downstream cascade induced by I-TBEV, while responses to the replicating virus were impacted by the inhibition of RIG-I-like, as well as Toll-like, receptors. Our results show that inactivated and live TBEV predominantly engaged an interferon response in our in vitro PBMC platform, and indicate RLRs as the main pattern recognition receptors involved in I-TBEV sensing.

Original languageEnglish
Article number664
Number of pages23
JournalVaccines
Volume9
Issue number6
DOIs
Publication statusPublished - 17-Jun-2021

Keywords

  • tick-borne encephalitis virus
  • TBE vaccine
  • peripheral blood mononuclear cells
  • RNA sequencing
  • interferon
  • RIG-I
  • TLR
  • YELLOW-FEVER VACCINE
  • FUNCTIONAL-ANALYSIS
  • ANTIBODY-RESPONSES
  • INFLUENZA VACCINE
  • SYSTEMS BIOLOGY
  • STRANDED-RNA
  • CELLS
  • TBE

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