vIRF3 encoded by Kaposi's sarcoma-associated herpesvirus inhibits T-cell factor-dependent transcription via a CREB-binding protein-interaction motif.
Kaposi's sarcoma-associated herpesvirus (KSHV) is an etiological agent of Kaposi's sarcoma and primary effusion lymphoma. Like other herpesviruses, KSHV has two distinct life cycles: latent and lytic. Among KSHV latent genes, viral interferon regulatory factor 3 (vIRF3), which shares homology with cellular IRFs, is a multifunctional protein. To identify unknown functions of vIRF3, we performed luciferase-reporter assays in the presence of vIRF3. These analyses revealed that overexpression of vIRF3 inhibited T-cell factor (TCF)-dependent transcriptional activity. This TCF-dependent transcription was associated with the Wnt signaling pathway, which normally regulates embryonic development, but contributes to oncogenesis under dysregulated conditions. Using a mutagenesis analysis, we identified a CREB-binding protein-interaction motif (LXXLL) in vIRF3 as an important region for its inhibitory activity. Collectively, our findings provide insight into the dysregulation of host signaling pathways in KSHV-infected cells.
Department of Life Science, Dongguk University-Seoul, Goyang 10326, South Korea.
Seho
S
Cha
Department of Biological Sciences, Korea Advanced Institute of Science and Technology, Daejeon 34141, South Korea.
Joonho
J
Choe
Department of Life Science, Dongguk University-Seoul, Goyang 10326, South Korea. Electronic address: tseo@dongguk.edu.
Taegun
T
Seo
D020816:Amino Acid Motifs; D050882:CREB-Binding Protein / Q000737:chemistry*; D002467:Cell Nucleus / Q000378:metabolism; D057809:HEK293 Cells; D019288:Herpesvirus 8, Human / Q000378:metabolism / Q000502:physiology*; D054884:Host-Pathogen Interactions / Q000235:genetics*; D006801:Humans; D050835:Interferon Regulatory Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D009154:Mutation; D051820:TCF Transcription Factors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D014158:Transcription, Genetic; D014764:Viral Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017735:Virus Latency; D060449:Wnt Signaling Pathway; D051176:beta Catenin / Q000378:metabolism
D050835:Interferon Regulatory Factors; D051820:TCF Transcription Factors; D014764:Viral Proteins; D051176:beta Catenin; C413486:viral interferon regulatory factors; D050882:CREB-Binding Protein
KSHV; TCF-dependent transcription; Wnt signaling pathway; vIRF3