Pteropus vampyrus TRIM40 Is an Interferon-Stimulated Gene That Antagonizes RIG-I-like Receptors

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.