MAVI1, an Endoplasmic Reticulum-localized Microprotein, Suppresses Antiviral Innate Immune Response by Targeting MAVS on Mitochondrion
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ABSTRACT:
PROVIDER: PRJNA913428 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR22797096_1.fastq.gz | Fastqsanger.gz | |||
| SRR22797096_2.fastq.gz | Fastqsanger.gz | |||
| SRR22797097_1.fastq.gz | Fastqsanger.gz | |||
| SRR22797097_2.fastq.gz | Fastqsanger.gz |
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Project description:Pattern recognition receptors (PRRs)-mediated innate immune responses are critical for host defense against microbial pathogens including RNA/DNA viruses. A growing number of coding genes and genes originally defined as non-coding RNAs (ncRNAs) are found to encode short peptides or proteins, named microproteins. However, the landscape of microproteins in responsive to virus infection and the functions of these microproteins remain uncharacterized. Here, we systematically identified microproteins, both from coding and non-coding genes, that are responsive to Vesicular Stomatitis Virus (VSV) infection. Among which, a highly conserved, endoplasmic reticulum (ER) membrane-localized microprotein, , MAVI1 (microprotein in antiviral immunity 1), was found to interact with mitochondrial localized MAVS protein, inhibiting the aggregation of MAVS and the activation of downstream type I interferon (IFN) signaling pathway. The critical role of MAVI1 was highlighted that viral infection was significantly attenuated and survival rate was significantly increased in Mavi1 knockout mice in vivo. A peptide inhibitor targeting the interaction between MAVI1 and MAVS is potent in activating the type I IFN signaling and defending viral infection both in vitro and in vivo. Our findings uncovered that microproteins could play critical roles in regulating antiviral innate immune responses via cross-organelle interaction, and targeting microproteins might represent a potential therapeutic avenue for treating viral infection in clinic.
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Project description:Pattern recognition receptors (PRRs)-mediated innate immune responses are critical for host defense against microbial pathogens including RNA/DNA viruses. A growing number of coding genes and genes originally defined as non-coding RNAs (ncRNAs) are found to encode short peptides or proteins, named microproteins. However, the landscape of microproteins in responsive to virus infection and the functions of these microproteins remain uncharacterized. Here, we systematically identified microproteins, both from coding and non-coding genes, that are responsive to Vesicular Stomatitis Virus (VSV) infection. Among which, a highly conserved, endoplasmic reticulum (ER) membrane-localized microprotein, , MAVI1 (microprotein in antiviral immunity 1), was found to interact with mitochondrial localized MAVS protein, inhibiting the aggregation of MAVS and the activation of downstream type I interferon (IFN) signaling pathway. The critical role of MAVI1 was highlighted that viral infection was significantly attenuated and survival rate was significantly increased in MAVI1 knockout mice in vivo. A peptide inhibitor targeting the interaction between MAVI1 and MAVS is potent in activating the type I IFN signaling and defending viral infection both in vitro and in vivo. Our findings uncovered that microproteins could play critical roles in regulating antiviral innate immune responses via cross-organelle interaction, and targeting microproteins might represent a potential therapeutic avenue for treating viral infection in clinic.
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Project description:Pattern recognition receptor-mediated innate immunity is critical for host defense against viruses. A growing number of coding and noncoding genes are found to encode microproteins. However, the landscape and functions of microproteins in responsive to virus infection remain uncharacterized. Here, we systematically identified microproteins that are responsive to vesicular stomatitis virus infection. A conserved and endoplasmic reticulum-localized membrane microprotein, MAVI1 (microprotein in antiviral immunity 1), was found to interact with mitochondrion-localized MAVS protein and inhibit MAVS aggregation and type I interferon signaling activation. The importance of MAVI1 was highlighted that viral infection was attenuated and survival rate was increased in Mavi1-knockout mice. A peptide inhibitor targeting the interaction between MAVI1 and MAVS activated the type I interferon signaling to defend viral infection. Our findings uncovered that microproteins play critical roles in regulating antiviral innate immune responses, and targeting microproteins might represent a therapeutic avenue for treating viral infection.
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