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Differentiation-Dependent KLF4 Expression Promotes Lytic Epstein-Barr Virus Infection in Epithelial Cells
Lytic EBV infection of differentiated oral epithelial cells results in the release of infectious viral particles and is required for efficient transmission of EBV from host to host. Lytic infection also causes a tongue lesion known as oral hairy leukoplakia (OHL). However, surprisingly little is known in regard to how EBV gene expression is regulated in epithelial cells. Using a stably EBV - infected, telomerase-immortalized normal oral keratinocyte cell line, we show here that undifferentiated basal epithelial cells support latent EBV infection, while differentiation of epithelial cells promotes lytic reactivation. Furthermore, we demonstrate that the KLF4 cellular transcription factor, which is required for normal epithelial cell differentiation and is expressed in differentiated, but not undifferentiated, normal epithelial cells, induces lytic EBV reactivation by activating transcription from the two EBV immediate-early gene promoters. We also show that the combination of KLF4 and another differentiation-dependent cellular transcription factor, BLIMP1, synergistically activates lytic gene expression in epithelial cells. We confirm that KLF4 and BLIMP1 expression in normal tongue epithelium is confined to differentiated cells, and that KLF4 and BLIMP1 are expressed in a patient-derived OHL tongue lesion. These results suggest that differentiation-dependent expression of KLF4 and BLIMP1 in epithelial cells promotes lytic EBV infection.
Vyšlo v časopise: Differentiation-Dependent KLF4 Expression Promotes Lytic Epstein-Barr Virus Infection in Epithelial Cells. PLoS Pathog 11(10): e32767. doi:10.1371/journal.ppat.1005195
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.ppat.1005195Souhrn
Lytic EBV infection of differentiated oral epithelial cells results in the release of infectious viral particles and is required for efficient transmission of EBV from host to host. Lytic infection also causes a tongue lesion known as oral hairy leukoplakia (OHL). However, surprisingly little is known in regard to how EBV gene expression is regulated in epithelial cells. Using a stably EBV - infected, telomerase-immortalized normal oral keratinocyte cell line, we show here that undifferentiated basal epithelial cells support latent EBV infection, while differentiation of epithelial cells promotes lytic reactivation. Furthermore, we demonstrate that the KLF4 cellular transcription factor, which is required for normal epithelial cell differentiation and is expressed in differentiated, but not undifferentiated, normal epithelial cells, induces lytic EBV reactivation by activating transcription from the two EBV immediate-early gene promoters. We also show that the combination of KLF4 and another differentiation-dependent cellular transcription factor, BLIMP1, synergistically activates lytic gene expression in epithelial cells. We confirm that KLF4 and BLIMP1 expression in normal tongue epithelium is confined to differentiated cells, and that KLF4 and BLIMP1 are expressed in a patient-derived OHL tongue lesion. These results suggest that differentiation-dependent expression of KLF4 and BLIMP1 in epithelial cells promotes lytic EBV infection.
Zdroje
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- Dimensions of Horizontal Gene Transfer in Eukaryotic Microbial Pathogens
- Addressing the Complications of Ebola and Other Viral Hemorrhagic Fever Infections: Using Insights from Bacterial and Fungal Sepsis
- Time for Chocolate: Current Understanding and New Perspectives on Cacao Witches’ Broom Disease Research
- Ganglioside and Non-ganglioside Mediated Host Responses to the Mouse Polyomavirus
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- Respiratory Syncytial Virus Disease Is Mediated by Age-Variable IL-33
- TRIM21 Promotes cGAS and RIG-I Sensing of Viral Genomes during Infection by Antibody-Opsonized Virus
- Modeling the Effects of Vorinostat Reveals both Transient and Delayed HIV Transcriptional Activation and Minimal Killing of Latently Infected Cells
- Identification of a Novel Lipoprotein Regulator of Spore Germination
- Calcium Regulation of Hemorrhagic Fever Virus Budding: Mechanistic Implications for Host-Oriented Therapeutic Intervention
- Antigen-Specific Th17 Cells Are Primed by Distinct and Complementary Dendritic Cell Subsets in Oropharyngeal Candidiasis
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- Dengue Virus Infection of Requires a Putative Cysteine Rich Venom Protein
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- Fundamental Roles of the Golgi-Associated Aspartyl Protease, ASP5, at the Host-Parasite Interface
- Phenotypic and Functional Alterations in Circulating Memory CD8 T Cells with Time after Primary Infection
- Systematic Identification of Cyclic-di-GMP Binding Proteins in Reveals a Novel Class of Cyclic-di-GMP-Binding ATPases Associated with Type II Secretion Systems
- Influenza Transmission in the Mother-Infant Dyad Leads to Severe Disease, Mammary Gland Infection, and Pathogenesis by Regulating Host Responses
- Myeloid Cell Arg1 Inhibits Control of Arthritogenic Alphavirus Infection by Suppressing Antiviral T Cells
- The White-Nose Syndrome Transcriptome: Activation of Anti-fungal Host Responses in Wing Tissue of Hibernating Little Brown Myotis
- Influenza Virus Reassortment Is Enhanced by Semi-infectious Particles but Can Be Suppressed by Defective Interfering Particles
- Identification of the Mechanisms Causing Reversion to Virulence in an Attenuated SARS-CoV for the Design of a Genetically Stable Vaccine
- Differentiation-Dependent KLF4 Expression Promotes Lytic Epstein-Barr Virus Infection in Epithelial Cells
- The Histone Acetyltransferase Hat1 Regulates Stress Resistance and Virulence via Distinct Chromatin Assembly Pathways
- C-di-GMP Regulates Motile to Sessile Transition by Modulating MshA Pili Biogenesis and Near-Surface Motility Behavior in
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- Crystal Structure of the Human Cytomegalovirus Glycoprotein B
- Depletion of . GlmU from Infected Murine Lungs Effects the Clearance of the Pathogen
- Immunologic Control of Papillomavirus Type 1
- Requires Host Rab1b for Survival in Macrophages
- Structure Analysis Uncovers a Highly Diverse but Structurally Conserved Effector Family in Phytopathogenic Fungi
- PD-L1 Expression on Retrovirus-Infected Cells Mediates Immune Escape from CD8 T Cell Killing
- Phospho-dependent Regulation of SAMHD1 Oligomerisation Couples Catalysis and Restriction
- IL-4 Induced Innate CD8 T Cells Control Persistent Viral Infection
- Crystal Structures of a Piscine Betanodavirus: Mechanisms of Capsid Assembly and Viral Infection
- BCG Skin Infection Triggers IL-1R-MyD88-Dependent Migration of EpCAM CD11b Skin Dendritic cells to Draining Lymph Node During CD4+ T-Cell Priming
- Antigenic Characterization of the HCMV gH/gL/gO and Pentamer Cell Entry Complexes Reveals Binding Sites for Potently Neutralizing Human Antibodies
- Rescue of a Plant Negative-Strand RNA Virus from Cloned cDNA: Insights into Enveloped Plant Virus Movement and Morphogenesis
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- Structural and Functional Analysis of Murine Polyomavirus Capsid Proteins Establish the Determinants of Ligand Recognition and Pathogenicity
- The Dual Role of an ESCRT-0 Component HGS in HBV Transcription and Naked Capsid Secretion
- PLOS Pathogens
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Najčítanejšie v tomto čísle- Chronobiomics: The Biological Clock as a New Principle in Host–Microbial Interactions
- Interferon-γ: The Jekyll and Hyde of Malaria
- Crosslinking of a Peritrophic Matrix Protein Protects Gut Epithelia from Bacterial Exotoxins
- Antigen-Specific Th17 Cells Are Primed by Distinct and Complementary Dendritic Cell Subsets in Oropharyngeal Candidiasis
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