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Early observations suggesting biological interactions between TMV and mammalian cells date back several decades ( Beyond TMV, plant virusderived single-stranded RNA nanoparticles analogous to tobamoviruses can be internalized by primary human dendritic cells and induce type I interferon responses via TLR7/8-dependent pathways, showing that plant viral RNA can activate canonical innate antiviral signaling in human immune cells ( Independent metagenomic studies have further demonstrated that TMV can be detected in the human respiratory tract ( Taken together, these observations support the notion that exposure to TMV is not a rare or artifactual event, but rather represents a genuine environmental exposure with demonstrated capacity for cellular entry and innate immune engagement in vertebrate systems