PUBLICATION

Attenuation of Antiviral Immune Response Caused by Perturbation of TRIM25-Mediated RIG-I Activation under Simulated Microgravity

Authors

Zhu, L., Nie, L., Xie, S., Li, M., Zhu, C., Qiu, X., Kuang, J., Liu, C., Lu, C., Li, W., Meng, E., Zhang, D., Zhu, L.

ID

ZDB-PUB-210109-10

Date

2021

Source

Cell Reports 34: 108600 (Journal)

Registered Authors

Keywords

K63-linked ubiquitination, RIG-I, TRIM25, antiviral immunity, positive feedback loop, rotary cell culture system, simulated microgravity, type I interferon, zebrafish embryo model

Datasets

GEO:GSE145967

MeSH Terms

Humans
Female
Toll-Like Receptors/immunology*
Toll-Like Receptors/metabolism
Ubiquitination
Disease Models, Animal
Gene Expression Profiling
Ubiquitin-Protein Ligases/immunology*
Ubiquitin-Protein Ligases/metabolism
Weightlessness/adverse effects*
Immunity*
Aerospace Medicine
HEK293 Cells
Male
Rhabdoviridae/immunology*
Zebrafish/immunology*
Zebrafish/metabolism
Signal Transduction
Animals
DEAD Box Protein 58/immunology*
DEAD Box Protein 58/metabolism
Rhabdoviridae Infections/veterinary
Rhabdoviridae Infections/virology

PubMed

33406425 Full text @ Cell Rep.

Abstract

Microgravity is a major environmental factor of space flight that triggers dysregulation of the immune system and increases clinical risks for deep-space-exploration crews. However, systematic studies and molecular mechanisms of the adverse effects of microgravity on the immune system in animal models are limited. Here, we establish a ground-based zebrafish disease model of microgravity for the research of space immunology. RNA sequencing analysis demonstrates that the retinoic-acid-inducible gene (RIG)-I-like receptor (RLR) and the Toll-like receptor (TLR) signaling pathways are significantly compromised by simulated microgravity (Sμg). TRIM25, an essential E3 for RLR signaling, is inhibited under Sμg, hampering the K63-linked ubiquitination of RIG-I and the following function-induction positive feedback loop of antiviral immune response. These mechanisms provide insights into better understanding of the effects and principles of microgravity on host antiviral immunity and present broad potential implications for developing strategies that can prevent and control viral diseases during space flight.

Genes / Markers

Figures