Non-Cytopathic Mammalian Orthoreovirus Infection Triggers Innate Immune Responses in Human Tonsil-Derived Mesenchymal Stem Cells: Implications for Cell Therapy Quality Control.

backgroundTonsil-derived mesenchymal stem cells (TMSCs) are widely used in regenerative medicine due to their high proliferative capacity and differentiation potential. However, their origin from immunological gateways exposes them to pathogens, raising concern about viral contamination during cell preparation. Understanding how these pathogens affect the biological and immunological properties of TMSCs is crucial for ensuring the safety and consistency of cell-based therapies. This study evaluated TMSC susceptibility and molecular responses to mammalian orthoreovirus (MRV).

methodsMRV infectivity in TMSCs and the innate immune responses were investigated using RNA-seq. Viral replication was confirmed by viral titration, L1 segment RT-PCR, and transcriptome mapping. Cellular impact was assessed using Live/Dead assays and protein-protein interaction network analysis.

resultsTMSCs were infected with MRV strains to evaluate their susceptibility. Although no significant cytopathic effects were observed, the cells exhibited high viral permissivity to MRV, with stable viral titers of 3.9-5.5 log TCID

conclusionMRV establishes a permissive but non-cytopathic infection in TMSCs, triggering innate immune activation through upregulation of IL1B, ISG15, and RSAD2. This virus-induced shift from a quiescent to an immunomodulatory phenotype may compromise therapeutic consistency. Because visual quality control fails to detect latent infections, rigorous viral monitoring during TMSC preparation is essential to ensure safety in clinical applications.