Translational selenium nanoparticles boost GPx1 activation to reverse HAdV-14 virus-induced oxidative damage

Area of Science:

• Biomedical Engineering
• Nanomedicine
• Virology

Background:

• Human adenovirus (HAdV) infections pose significant risks, especially in immunocompromised individuals.
• Current treatments for HAdV are limited by toxicity and low efficacy.
• Selenium's antiviral potential can be enhanced through optimized speciation.

Purpose of the Study:

• To investigate the anti-HAdV effects of different selenium (Se) speciation.
• To evaluate lentinan (LNT)-decorated selenium nanoparticles (SeNPs@LNT) as a potential antiviral agent against HAdV.
• To elucidate the underlying mechanisms of SeNPs@LNT in combating HAdV infection.

Main Methods:

• Synthesis and characterization of lentinan-decorated selenium nanoparticles (SeNPs@LNT).
• In vitro assessment of SeNPs@LNT's cytotoxicity and anti-HAdV activity.
• Analysis of SeNPs@LNT's effects on mitochondrial damage, reactive oxygen species (ROS) production, DNA damage, and apoptosis signaling pathways.
• In vivo studies in Se-deficient mice to evaluate SeNPs@LNT's efficacy in treating adenovirus pneumonia.

Main Results:

• SeNPs@LNT demonstrated excellent anti-HAdV activity with low cytotoxicity.
• SeNPs@LNT reduced HAdV-induced mitochondrial damage, ROS production, and viral DNA replication.
• SeNPs@LNT modulated the p53/Bcl-2 pathway to inhibit apoptosis and repaired host cell DNA damage.
• In vivo, SeNPs@LNT targeted infected sites, enhanced Glutathione peroxidase 1 (GPx1) synthesis, and alleviated inflammatory cytokine storm in Se-deficient mice.

Conclusions:

• SeNPs@LNT represents an optimized selenium speciation with significant anti-HAdV efficacy.
• The mechanism involves antioxidant, anti-apoptotic, and DNA repair pathways, alongside immunomodulation via GPx1.
• SeNPs@LNT is a promising pharmaceutical candidate for treating human adenovirus infections and pneumonia.