Genetically Encoded Near-Infrared Fluorescent Proteins for Viral Imaging and Detection: A Mini-Review

Bacteriophytochrome-derived near-infrared fluorescent proteins (NIR FPs) provide deep tissue penetration, low autofluorescence, and endogenous biliverdin compatibility, enabling non-invasive visualization of viral processes in living systems. Engineering advances (iRFPs, monomeric miRFPs, photoactivatable PAiRFPs) have improved brightness, stability, and genetic encodability for robust use in mammalian models. These reporters support real-time tracking of infection dynamics and host-virus interactions and power diagnostic platforms including reporter viruses, CRISPR-based assays, and nanotechnology-enhanced biosensors. Multimodal integration with photoacoustic tomography and PET further extends their translational utility. Remaining challenges include brightness/photostability limits and the need for broader translational validation, yet progress in structure-guided mutagenesis, computational/AI-assisted protein design, and hybrid imaging strategies promises to close these gaps. This mini-review synthesizes the design principles, viral imaging/detection use cases, and translational prospects of bacteriophytochrome-derived NIR FPs, highlighting their potential to advance viral surveillance, therapeutic evaluation, and precision diagnostics.