Unveiling the role of KSHV-infected human mesenchymal stem cells in Kaposi's sarcoma initiation

Ezequiel Lacunza, Anuj Ahuja, Omar A. Coso, Martin Abba, Juan Carlos Ramos, Ethel Cesarman, Enrique A. Mesri, Julian Naipauer

Research output: Contribution to journalArticlepeer-review

Abstract

Kaposi's sarcoma (KS) may derive from Kaposi's sarcoma herpesvirus (KSHV)-infected human mesenchymal stem cells (hMSCs) that migrate to sites characterized by inflammation and angiogenesis, promoting the initiation of KS. By analyzing the RNA sequences of KSHV-infected primary hMSCs, we have identified specific cell subpopulations, mechanisms, and conditions involved in the initial stages of KSHV-induced transformation and reprogramming of hMSCs into KS progenitor cells. Under proangiogenic environmental conditions, KSHV can reprogram hMSCs to exhibit gene expression profiles more similar to KS tumors, activating cell cycle progression, cytokine signaling pathways, endothelial differentiation, and upregulating KSHV oncogenes indicating the involvement of KSHV infection in inducing the mesenchymal-to-endothelial (MEndT) transition of hMSCs. This finding underscores the significance of this condition in facilitating KSHV-induced proliferation and reprogramming of hMSCs towards MEndT and closer to KS gene expression profiles, providing further evidence of these cell subpopulations as precursors of KS cells that thrive in a proangiogenic environment.

Original languageEnglish
Article numbere29684
JournalJournal of Medical Virology
Volume96
Issue number5
DOIs
StatePublished - May 2024
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2024 The Author(s). Journal of Medical Virology published by Wiley Periodicals LLC.

Keywords

  • Kaposi's sarcoma
  • KSHV
  • mesenchymal-to-endothelial transition

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