Insect SVWC Proteins: A Diverse Cytokine-like Family Orchestrating Multilayered Antiviral and Antibacterial Immunity

The single von Willebrand factor C (SVWC) domain-containing protein family represents a crucial class of immune molecules recently identified in insects and crustaceans. Initially regarded as functional analogs of vertebrate interferons (IFNs) due to their virus-induced expression and activation of the Janus kinase-signal transducer and activator of the transcription (JAK-STAT) pathway, recent studies have revealed that SVWC proteins possess far more complex functions. Many SVWC members are themselves a novel class of pattern recognition receptors (PRRs) that can directly bind to viruses and bacteria. Importantly, SVWCs are not a single entity but a highly diverse family-multiple subtypes exist in Drosophila, Bombyx mori, and shrimp-a gene expansion that implies functional differentiation. This review systematically examines the multifunctionality of SVWC proteins in insects and crustaceans, with a particular focus on the functional specialization driven by subtype diversity. We delve into the complex regulatory networks governing SVWC expression, including the differential activation by nuclear factor kappa B (NF-κB) pathways (Dorsal, Rel-2, Relish) and interferon regulatory factor (IRF) pathways. We detail the unique signaling mechanism by which SVWCs activate the JAK-STAT pathway via integrins, rather than the canonical Domeless receptor. Furthermore, we extend the discussion to the emerging roles of SVWCs as PRRs in humoral immunity (activating Toll/IMD pathways to induce antimicrobial peptides) and cellular immunity (mediating hemocyte phagocytosis). Based on current evidence, We propose that diverse SVWC subtypes may recognize distinct pathogens, bind to different integrin receptors, and activate specific STAT variants via disparate upstream induction pathways, thereby establishing a systematic and hierarchical immunoregulatory network. This understanding positions the SVWC protein family as a central hub in the insect immune network and offers a novel perspective on the complexity and evolution of invertebrate immunity.