Repression of interferon-α stimulated genes expression by Kaposi's sarcoma-associated herpesvirus K-bZIP protein

Kaposi's sarcoma-associated herpesvirus (KSHV) encodes a transcriptional repressor, K-bZIP. We previously demonstrated that K-bZIP suppresses interferon (IFN)-β expression. Here, we provide evidence that K-bZIP affects IFN signaling, resulting in impaired IFN-stimulated genes expression. Inhibition by K-bZIP is independent of the phosphorylation of signal transducers and activators of transcription proteins or the binding of the IFN-stimulated gene factor 3 to the IFN-stimulated responsive element. Relative to the wild-type protein, K-bZIPK158R mutant exhibited reduced inhibitory activity, indicating that sumoylation on K158 is likely important for this effect. A new sumoylation site present within a newly identified K-bZIP variant and absent from the fully spliced K-bZIP was also identified. Furthermore, K-bZIP is acetylated on lysine residues and CBP enhances K-bZIP acetylation. Combined with its ability to negatively modulate IFN-β production and inhibit type I IFN signaling, K-bZIP represents a viral immunomodulator that contributes to curtail immune defense mechanisms and favor KSHV's persistence.