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Peptidomic Analysis on Mouse Lung Tissue Reveals AGDP as a Potential Bioactive Peptide against Pseudorabies Virus
Yijie Ma1, Shimao Tian1, Qianhui Wan1
1Key Laboratory of Animal Pathogen Infection and Immunology of Fujian Province, College of Animal Sciences (College of Bee Science), Fujian Agricultural and Forestry University, Fuzhou 350002, China.
Abstract:
Pseudorabies virus (PRV) infection could cause severe histopathological damage via releasing multiple factors, including cytokines, peptides, etc. Here, peptidomic results showed that 129 peptides were identified in PRV-infected mouse lungs and were highly involved in the process of PRV infection. The role of one down-regulated biological peptide (designated as AGDP) during PRV infection was investigated. To verify the expression profiles of AGDP in response to PRV infection, the expression level of the precursor protein of AGDP mRNA was significantly decreased in PRV-infected mouse lungs and cells. The synthesized AGDP-treating cells were less susceptible to PRV challenges than the controls, as demonstrated by the decreased virus production and gE expression. AGDP not only inhibited the expression of TNF-α and IL-8 but also appeared to suppress the extracellular release of high-mobility group box 1 (HMGB1) by inhibiting the output of nuclear HMGB1 in cells. AGDP could also inhibit the degradation of IκBα and the phosphorylation levels of P65 after PRV infection. In total, our results revealed many meaningful peptides involved in PRV infection, thereby enhancing the current understanding of the host response to PRV infection, and how AGDP may serve as a promising candidate for developing novel anti-PRV drugs.
Insights
A novel peptide, AGDP, shows potential as an antiviral drug against Pseudorabies virus (PRV). AGDP treatment reduced PRV infection, inhibited inflammatory cytokines, and protected host cells.
Area of Science:
- Veterinary Virology
- Immunology
- Proteomics
Background:
- Pseudorabies virus (PRV) causes significant histopathological damage through various released factors.
- Peptidomic analysis reveals numerous peptides involved in PRV infection dynamics.
Purpose of the Study:
- To investigate the role of a down-regulated peptide, AGDP, in PRV infection.
- To explore AGDP's potential as a therapeutic agent against PRV.
Main Methods:
- Peptidomic analysis of PRV-infected mouse lungs.
- Verification of AGDP precursor mRNA expression levels.
- Assessing PRV susceptibility in AGDP-treated cells.
- Measuring cytokine expression (TNF-α, IL-8) and HMGB1 release.
- Analyzing IκBα degradation and P65 phosphorylation.
Main Results:
- AGDP precursor mRNA expression was significantly decreased in PRV-infected lungs and cells.
- AGDP treatment reduced PRV production and gE expression, indicating decreased susceptibility.
- AGDP inhibited TNF-α, IL-8, and extracellular HMGB1 release by suppressing nuclear HMGB1 output.
- AGDP suppressed PRV-induced IκBα degradation and P65 phosphorylation.
Conclusions:
- AGDP demonstrates significant antiviral activity against PRV.
- AGDP modulates host inflammatory responses and innate immunity pathways.
- AGDP represents a promising candidate for novel anti-PRV drug development.
