Extracellular vesicles from Kaposi Sarcoma-associated herpesvirus lymphoma induce long-term endothelial cell reprogramming

Autor: Anthony B. Eason, Aubrey Bailey, Blossom Damania, Kurtis M. Host, Jie Xiong, Justin T. Landis, Avery Cheves, Rachele Bigi, Zhe Ma, Lindsey M. Costantini, Ryan P. McNamara, Pauline E. Chugh, Dirk P. Dittmer, Jack D. Griffith
Rok vydání: 2019
Předmět:
MAPK/ERK pathway
Lymphoma
Physiology
viruses
Pathology and Laboratory Medicine
medicine.disease_cause
Biochemistry
Epithelium
Hematologic Cancers and Related Disorders
Spectrum Analysis Techniques
Animal Cells
Cell Movement
Immune Physiology
Tumor Virus
Virus latency
Medicine and Health Sciences
Biology (General)
Post-Translational Modification
Phosphorylation
Innate Immune System
0303 health sciences
030302 biochemistry & molecular biology
Cell migration
Hematology
Kaposi's Sarcoma-Associated Herpesvirus
Flow Cytometry
Cellular Reprogramming
Virus Latency
Cell biology
Nucleic acids
Cell Motility
Cell Transformation
Neoplastic
Oncology
Spectrophotometry
Medical Microbiology
Viral Pathogens
Viruses
Herpesvirus 8
Human
Host-Pathogen Interactions
Cytokines
Lymphomas
Cytophotometry
Pathogens
Cellular Types
Anatomy
Signal transduction
Research Article
Signal Transduction
Herpesviruses
QH301-705.5
Immunology
Cell Migration
Biology
Research and Analysis Methods
Microbiology
Extracellular Vesicles
Viral Proteins
03 medical and health sciences
Virology
Human Umbilical Vein Endothelial Cells
Genetics
Extracellular
medicine
Humans
Kaposi's sarcoma-associated herpesvirus
Non-coding RNA
Microbial Pathogens
Sarcoma
Kaposi
Molecular Biology
Cell Proliferation
030304 developmental biology
Natural antisense transcripts
Biology and life sciences
Organisms
Cancers and Neoplasms
Endothelial Cells
Proteins
Epithelial Cells
Cell Biology
RC581-607
Molecular Development
medicine.disease
Microvesicles
Gene regulation
MicroRNAs
Biological Tissue
Immune System
RNA
Parasitology
Gene expression
Immunologic diseases. Allergy
DNA viruses
Transcriptome
Developmental Biology
Zdroj: PLoS Pathogens
PLoS Pathogens, Vol 15, Iss 2, p e1007536 (2019)
ISSN: 1553-7374
Popis: Extracellular signaling is a mechanism that higher eukaryotes have evolved to facilitate organismal homeostasis. Recent years have seen an emerging interest in the role of secreted microvesicles, termed extracellular vesicles (EV) or exosomes in this signaling network. EV contents can be modified by the cell in response to stimuli, allowing them to relay information to neighboring cells, influencing their physiology. Here we show that the tumor virus Kaposi’s Sarcoma-associated herpesvirus (KSHV) hijacks this signaling pathway to induce cell proliferation, migration, and transcriptome reprogramming in cells not infected with the virus. KSHV-EV activates the canonical MEK/ERK pathway, while not alerting innate immune regulators, allowing the virus to exert these changes without cellular pathogen recognition. Collectively, we propose that KSHV establishes a niche favorable for viral spread and cell transformation through cell-derived vesicles, all while avoiding detection.
Author summary The role of extracellular vesicles (EV) has received considerable attention in recent years. The contents of these cell-derived vesicles have been shown to be modulated upon challenge by a virus or neoplastic transformation, and can influence the behavior of recipient cells. Here we demonstrate that purified EV from an AIDS-associated, virus-driven lymphoma induces unique cellular signaling, motility, and gene expression reprogramming in recipient endothelial cells. This was accomplished without activation of innate immune activation, even after prolonged exposure to these EV. Collectively our results point toward a model in which tumor-derived EV condition neighboring cell physiology, while avoiding detection by immune regulators.
Databáze: OpenAIRE
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