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Monitoring Activation of the Antiviral Pattern Recognition Receptors RIG-I And PKR By Limited Protease Digestion and Native PAGE
Published on: July 29, 2014
Pteropus vampyrus TRIM40 Is an Interferon-Stimulated Gene That Antagonizes RIG-I-like Receptors
Sarah van Tol1, Adam Hage1, Ricardo Rajsbaum1,2,3
1Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX 77555, USA.
Abstract:
Nipah virus (NiV; genus: Henipavirus; family: Paramyxoviridae) naturally infects Old World fruit bats (family Pteropodidae) without causing overt disease. Conversely, NiV infection in humans and other mammals can be lethal. Comparing bat antiviral responses with those of humans may illuminate the mechanisms that facilitate bats' tolerance. Tripartite motif proteins (TRIMs), a large family of E3-ubiquitin ligases, fine-tune innate antiviral immune responses, and two human TRIMs interact with Henipavirus proteins. We hypothesize that NiV infection induces the expression of an immunosuppressive TRIM in bat, but not human cells, to promote tolerance. Here, we show that TRIM40 is an interferon-stimulated gene (ISG) in pteropodid but not human cells. Knockdown of bat TRIM40 increases gene expression of IFNβ, ISGs, and pro-inflammatory cytokines following poly(I:C) transfection. In Pteropus vampyrus, but not human cells, NiV induces TRIM40 expression within 16 h after infection, and knockdown of TRIM40 correlates with reduced NiV titers as compared to control cells. Bats may have evolved to express TRIM40 in response to viral infections to control immunopathogenesis.
Insights
Fruit bats tolerate Nipah virus (NiV) infection by expressing TRIM40, an immune-suppressing protein. This finding reveals a key mechanism for bat virus tolerance, contrasting with lethal NiV outcomes in humans.
Area of Science:
- Virology
- Immunology
- Comparative genomics
Background:
- Nipah virus (NiV) causes lethal disease in humans but is tolerated by its natural reservoir, Old World fruit bats (Pteropodidae).
- Tripartite motif (TRIM) proteins are E3 ubiquitin ligases crucial for innate antiviral immunity, with some TRIMs known to interact with henipaviruses.
Purpose of the Study:
- To investigate the hypothesis that NiV induces an immunosuppressive TRIM in bats, promoting viral tolerance.
- To compare TRIM expression and function in bat versus human cells during NiV infection and response to innate immune stimuli.
Main Methods:
- Assessed TRIM40 as an interferon-stimulated gene (ISG) in pteropodid and human cells.
- Utilized TRIM40 knockdown in bat cells to evaluate its role in antiviral responses to poly(I:C) and NiV infection.
- Quantified NiV titers in bat cells with and without TRIM40 knockdown.
Main Results:
- TRIM40 is an ISG in pteropodid cells but not human cells.
- Knockdown of bat TRIM40 enhanced the expression of IFNβ, ISGs, and pro-inflammatory cytokines after poly(I:C) stimulation.
- NiV infection upregulated TRIM40 in bat cells within 16 hours, and TRIM40 knockdown reduced NiV titers.
Conclusions:
- Bats may have evolved TRIM40 expression as a mechanism to control viral immunopathogenesis and tolerate NiV infection.
- TRIM40 plays a significant role in facilitating NiV tolerance in fruit bats.
- Understanding bat antiviral strategies offers insights into potential therapeutic targets for NiV and other paramyxoviruses.
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