Aggregation potency and proinflammatory effects of SARS-CoV-2 proteins.

Area of Science:

• Neuroscience
• Virology
• Cell Biology

Background:

• Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, is recognized as a respiratory illness.
• Emerging evidence indicates persistent neurological effects and potential neurodegeneration following SARS-CoV-2 infection.
• The precise mechanisms underlying SARS-CoV-2-induced nervous system damage remain largely unknown.

Purpose of the Study:

• To investigate shared cellular pathways contributing to SARS-CoV-2-induced neural dysfunction and neurodegeneration.
• To explore the roles of protein aggregation and inflammatory responses in viral-induced neurological damage.
• To identify potential therapeutic targets for mitigating long-term COVID-19 neurological consequences.

Main Methods:

• Examined the expression and distribution of ten SARS-CoV-2 proteins in two distinct cell lines.
• Assessed the induction of protein aggregation and pro-inflammatory responses by viral proteins.
• Investigated the impact of viral protein expression on endoplasmic reticulum (ER) stress and the autophagy-lysosome pathway.

Main Results:

• Observed distinct expression patterns of SARS-CoV-2 proteins, leading to protein aggregation and pro-inflammatory cytokine release.
• Found that viral protein expression induced ER stress and inhibited the autophagy-lysosome pathway.
• Demonstrated that enhancing autophagy function reduced viral protein aggregation.

Conclusions:

• SARS-CoV-2 proteins can induce neural dysfunction and neurodegeneration through mechanisms involving protein aggregation and inflammation.
• Inhibition of the autophagy-lysosome pathway is a key cellular response to SARS-CoV-2 protein expression.
• Modulating autophagy and proteostasis presents a promising therapeutic strategy to counteract long-lasting cytotoxic effects of SARS-CoV-2.