Persistent Inflammation, Maladaptive Remodeling, and Fibrosis in the Kidney Following Long COVID-like MHV-1 Mouse...

Area of Science:

• Molecular biology
• Renal pathophysiology
• Virology

Background:

• SARS-CoV-2 infection is linked to long-term kidney damage.
• Understanding the molecular mechanisms of kidney complications is crucial.
• A murine model of MHV-1-induced SARS-like illness was used to study chronic kidney changes.

Purpose of the Study:

• To characterize long-term kidney transcriptomic changes after coronavirus infection.
• To evaluate the therapeutic efficacy of SPIKENET (SPK) in mitigating these changes.

Main Methods:

• Infection of A/J mice with MHV-1, followed by renal tissue collection.
• Immunofluorescence and Next Generation RNA Sequencing for gene expression analysis.
• Bioinformatic analyses (PCA, volcano plots, GO/KEGG) and real-time PCR validation.
• Assessment of SPK treatment efficacy through comparative transcriptomic profiling.

Main Results:

• Long-term MHV-1 infection sustained upregulation of genes involved in inflammation, fibrosis, muscle regeneration, and cytoskeletal remodeling.
• Reduced expression and variability of proximal tubule transporters (SLC22, SLC22A8) indicated loss of segment-specific identity.
• Downregulation of SLC12A1 was associated with polyuria and hydronephrosis, suggesting tubular dysfunction and a pro-fibrotic phenotype.
• SPK treatment reversed most gene expression changes, restoring profiles similar to control mice.

Conclusions:

• MHV-1-induced long COVID causes persistent kidney transcriptional reprogramming, marked by chronic inflammation, cytoskeletal dysregulation, and fibrogenesis.
• SPK demonstrated significant therapeutic potential by normalizing molecular signatures and preventing long-term renal damage.
• The MHV-1 model is relevant for studying COVID-19-associated renal sequelae, and SPK warrants further investigation as a potential therapy.