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

Hye-Ra Lee; Jaba Mitra; Stacy Lee; Shou-Jiang Gao; Tae-Kwang Oh; Myung Hee Kim; Taekjip Ha; Jae U Jung

doi:10.1128/JVI.01897-15

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

J Virol. 2015 Oct 21;90(2):1139-43. doi: 10.1128/JVI.01897-15. Print 2016 Jan 15.

Authors

Hye-Ra Lee¹, Jaba Mitra², Stacy Lee³, Shou-Jiang Gao³, Tae-Kwang Oh⁴, Myung Hee Kim⁴, Taekjip Ha², Jae U Jung⁵

Affiliations

¹ 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.
² 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.
³ Department of Molecular Microbiology and Immunology, Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
⁴ Infection and Immunity Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, South Korea.
⁵ 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.

Abstract

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cell Cycle Checkpoints*
Down-Regulation
Genes, bcl-1*
Herpesvirus 8, Human / physiology*
Host-Pathogen Interactions*
Interferon Regulatory Factors / metabolism*
Peptide Fragments / antagonists & inhibitors*
Sialoglycoproteins / antagonists & inhibitors*
Viral Proteins / metabolism*
Virus Replication
beta Catenin / antagonists & inhibitors*

Substances

CTNNB1 protein, human
Interferon Regulatory Factors
Peptide Fragments
Sialoglycoproteins
Viral Proteins
beta Catenin
bone sialoprotein (35-62), human
viral interferon regulatory factors

Abstract

Publication types

MeSH terms

Substances

Grants and funding