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

Vaccines

Jeroen L. A. Pennings¹  Marilena P. Etna²  Eliana M. Coccia²  Anke Huckriede³  Aurora Signorazzi³  Malou Noya³ 

[1] Centre for Health Protection, National Institute for Public Health and the Environment (RIVM), 3721MA Bilthoven, The Netherlands;Department of Infectious Diseases, Istituto Superiore di Sanità, 000161 Rome, Italy;Department of Medical Microbiology & Infection Prevention, University Medical Center Groningen, University of Groningen, 9713GZ Groningen, The Netherlands;

关键词: tick-borne encephalitis virus;    TBE vaccine;    peripheral blood mononuclear cells;    RNA sequencing;    interferon;    RIG-I;   

DOI  :  10.3390/vaccines9060664

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown