MAVI1, an endoplasmic reticulum-localized microprotein, suppresses antiviral innate immune response by targeting MAVS...

Area of Science:

• Immunology
• Molecular Biology
• Virology

Background:

• Innate immunity, mediated by pattern recognition receptors, is crucial for antiviral defense.
• Microproteins, encoded by numerous genes, have largely uncharacterized roles in viral infection responses.
• Understanding microprotein functions in antiviral immunity is essential for developing new therapies.

Purpose of the Study:

• To systematically identify microproteins involved in the response to vesicular stomatitis virus infection.
• To characterize the function and mechanism of a novel microprotein, MAVI1, in antiviral immunity.
• To explore the therapeutic potential of targeting microproteins in viral infections.

Main Methods:

• Systematic identification of microproteins responsive to vesicular stomatitis virus.
• Characterization of MAVI1's localization, interaction with MAVS, and effect on type I interferon signaling.
• Assessment of MAVI1's role in vivo using Mavi1-knockout mice and a peptide inhibitor targeting MAVI1-MAVS interaction.

Main Results:

• MAVI1, an endoplasmic reticulum-localized microprotein, was identified as a key regulator of antiviral innate immunity.
• MAVI1 interacts with MAVS, inhibiting its aggregation and subsequent type I interferon signaling.
• Mavi1-knockout mice exhibited attenuated viral infection and increased survival rates.
• A peptide inhibitor targeting MAVI1-MAVS interaction successfully activated type I interferon signaling for antiviral defense.

Conclusions:

• Microproteins play significant roles in modulating antiviral innate immune responses.
• MAVI1 acts as a negative regulator of type I interferon signaling during viral infection.
• Targeting microproteins, such as MAVI1, represents a promising therapeutic strategy for viral infections.