Figure 3. Mechanistic overview of the antiviral defense pathway mediated by NIK1. Upon virus infection, NIK1 forms a homodimer and is activated through transphosphorylation of its kinase domain at the Thr-474 residue. Alternatively, NIK1 binds to an unknown ligand-binding LRR-RLK in a stimulus-dependent manner. The activation of NIK1 triggers the phosphorylation of RPL10 that, in turn, is transported to the nucleus. In the nuclear compartment, RPL10 interacts with LIMYB, which binds to the promoter of ribosomal protein (RP) genes to repress their transcription. As a consequence, a suppression of host global protein synthesis is observed, which also impairs translation of viral mRNA. As a defense countermeasure, NSP of begomoviruses binds and inhibits the NIK1 kinase activity, which impairs the RPL10 phosphorylation. Thus, RPL10 is retained in the cytosol, enhancing begomovirus infection. As begomoviruses have single-stranded circular DNA genomes, they replicate in the nucleus of the infected cells by double-stranded DNA intermediaries, which are also template for transcription of viral mRNAs. NSP binds to nascent viral DNA and facilitates the traffic of viral DNA from the nucleus to the cytoplasm by an unclear mechanism.