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Simultaneous neutralization and innate immune detection of a replicating virus by TRIM21
R E Watkinson1, J C H Tam, M J Vaysburd
1Medical Research Council Laboratory of Molecular Biology, Division of Protein and Nucleic Acid Chemistry, Cambridge Biomedical Campus, Cambridge, United Kingdom.
Journal of Virology
|April 19, 2013
Summary
Tripartite motif-containing 21 (TRIM21) protein blocks viral spread and activates immunity. Inhibiting TRIM21 or its related pathways significantly increases viral infection, highlighting TRIM21's crucial role in antiviral defense.
Area of Science:
- Immunology
- Virology
- Cell Biology
Background:
- Tripartite motif-containing 21 (TRIM21) functions as a cytosolic immunoglobulin receptor.
- TRIM21 mediates antibody-dependent intracellular neutralization (ADIN).
Purpose of the Study:
- To investigate the role of TRIM21 in inhibiting viral spreading infection.
- To determine if TRIM21 activates innate immunity during viral infection.
Main Methods:
- Quantitative PCR (qPCR) assay to measure in vitro replication of mouse adenovirus type 1 (MAV-1).
- Genetic ablation of TRIM21 and chemical inhibition of p97/VCP or proteasome.
- Measurement of proinflammatory cytokine secretion (TNF-α and IL-6).
Main Results:
- Genetic or chemical inhibition of TRIM21 pathways increased MAV-1 infection by over 1,000-fold in the presence of immune serum.
- TRIM21-mediated antibody neutralization of viral replication was observed in immunized mice.
- TRIM21 activation led to secretion of TNF-α and IL-6.
Conclusions:
- TRIM21 provides a potent defense against spreading viral infections.
- TRIM21 plays a significant role in inducing an antiviral state and activating innate immunity.
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