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.
Lefort
Sylvain
S
Laboratory of Virology, Rheumatology and Immunology Research Center, CHUQ Research Center and Faculty of Medicine, Laval University, 2705 Laurier Boulevard, Quebec City, Quebec, Canada.
Gravel
Annie
A
Flamand
Louis
L
D000595:Amino Acid Sequence; D019943:Amino Acid Substitution; D001120:Arginine / Q000235:genetics; D001483:Base Sequence; D050976:Basic-Leucine Zipper Transcription Factors / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D002460:Cell Line; D019288:Herpesvirus 8, Human / Q000276:immunology / Q000472:pathogenicity*; D006801:Humans; D057131:Immune Evasion; D016898:Interferon-alpha / Q000037:antagonists & inhibitors* / Q000276:immunology*; D008239:Lysine / Q000235:genetics; D008969:Molecular Sequence Data; D020125:Mutation, Missense; D011499:Protein Processing, Post-Translational; D011506:Proteins; D012097:Repressor Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*; D014764:Viral Proteins / Q000235:genetics / Q000276:immunology / Q000502:physiology*
D050976:Basic-Leucine Zipper Transcription Factors; D016898:Interferon-alpha; C118265:K8 protein, Human herpesvirus 8; D011506:Proteins; D012097:Repressor Proteins; D014764:Viral Proteins; D001120:Arginine; D008239:Lysine