Kaposi's Sarcoma-Associated Herpesvirus Viral Interferon Regulatory Factor 4 (vIRF4) Perturbs the G1-S Cell Cycle Progression via Deregulation of the cyclin D1 Gene.
Kaposi's sarcoma-associated herpesvirus (KSHV) infection modulates the host cell cycle to create an environment optimal for its viral-DNA replication during the lytic life cycle. We report here that KSHV vIRF4 targets the β-catenin/CBP cofactor and blocks its occupancy on the cyclin D1 promoter, suppressing the G1-S cell cycle progression and enhancing KSHV replication. This shows that KSHV vIRF4 suppresses host G1-S transition, possibly providing an intracellular milieu favorable for its replication.
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA hyelee@usc.edu jaeujung@med.usc.edu.
Hye-Ra
HR
Lee
Department of Physics, Center for the Physics of Living Cells and Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
Jaba
J
Mitra
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Stacy
S
Lee
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Shou-Jiang
SJ
Gao
Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.
Tae-Kwang
TK
Oh
Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.
Myung Hee
MH
Kim
Department of Physics, Center for the Physics of Living Cells and Carl R. Woese Institute for Genomic Biology, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA.
Taekjip
T
Ha
Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, USA hyelee@usc.edu jaeujung@med.usc.edu.
Jae U
JU
Jung
D059447:Cell Cycle Checkpoints; D015536:Down-Regulation; D019940:Genes, bcl-1; D019288:Herpesvirus 8, Human / Q000502:physiology*; D054884:Host-Pathogen Interactions; D050835:Interferon Regulatory Factors / Q000378:metabolism*; D010446:Peptide Fragments / Q000037:antagonists & inhibitors*; D012795:Sialoglycoproteins / Q000037:antagonists & inhibitors*; D014764:Viral Proteins / Q000378:metabolism*; D014779:Virus Replication; D051176:beta Catenin / Q000037:antagonists & inhibitors*
C495270:CTNNB1 protein, human; D050835:Interferon Regulatory Factors; D010446:Peptide Fragments; D012795:Sialoglycoproteins; D014764:Viral Proteins; D051176:beta Catenin; C571744:bone sialoprotein (35-62), human; C413486:viral interferon regulatory factors