Guinea Pig Interferon-Alpha (IFN-α) is a type I interferon produced primarily by plasmacytoid dendritic cells and virus-infected cells in guinea pigs (Cavia porcellus), where it serves as a key mediator of early innate antiviral immunity. Upon binding to the type I interferon receptor complex (IFNAR1/IFNAR2), guinea pig IFN-α activates JAK/STAT signaling pathways, leading to induction of interferon-stimulated genes (ISGs) that inhibit viral replication, enhance antigen presentation, and promote activation of natural killer (NK) cells and adaptive immune responses. IFN-α plays an important role in guinea pig models of infectious diseases, including influenza virus, Lassa virus, Ebola virus (adapted strains), cytomegalovirus, and other viral pathogens, where interferon responses influence viral control, inflammation, and disease outcome. Because guinea pigs are widely used as translational models for respiratory infections and viral hemorrhagic fevers, characterization of IFN-α is essential for understanding antiviral defense mechanisms, immune-mediated pathology, vaccine efficacy, and antiviral therapeutic strategies. As both a biomarker and functional regulator of host–virus interactions, guinea pig IFN-α supports comparative immunology research and preclinical evaluation of countermeasures relevant to human infectious diseases.