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

PLoS Pathog. 2019 Feb 4;15(2):e1007536. doi: 10.1371/journal.ppat.1007536. eCollection 2019 Feb.


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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Cell Movement
  • Cell Proliferation
  • Cell Transformation, Neoplastic / metabolism
  • Cellular Reprogramming / genetics
  • Cellular Reprogramming / physiology*
  • Endothelial Cells / physiology
  • Extracellular Vesicles / physiology*
  • Herpesvirus 8, Human / genetics
  • Herpesvirus 8, Human / metabolism*
  • Host-Pathogen Interactions
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Lymphoma / genetics
  • Lymphoma / metabolism
  • Sarcoma, Kaposi / metabolism
  • Sarcoma, Kaposi / virology
  • Signal Transduction
  • Transcriptome / genetics
  • Viral Proteins
  • Virus Latency


  • Viral Proteins