PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment

Julian Naipauer, Santas Rosario, Sachin Gupta, Courtney Premer, Omayra Méndez-Solís, Mariana Schlesinger, Virginia Ponzinibbio, Vaibhav Jain, Lauren Gay, Rolf Renne, Ho Lam Chan, Lluis Morey, Daria Salyakina, Martin Abba, Sion Williams, Joshua M. Hare, Pascal J. Goldschmidt-Clermont, Enrique A. Mesri

Research output: Contribution to journalArticle

3 Scopus citations

Abstract

Kaposi's sarcoma (KS) is an AIDS-defining cancer caused by the KS-associated herpesvirus (KSHV). Unanswered questions regarding KS are its cellular ontology and the conditions conducive to viral oncogenesis. We identify PDGFRA(+)/SCA-1(+) bone marrow-derived mesenchymal stem cells (Pα(+)S MSCs) as KS spindle-cell progenitors and found that proangiogenic environmental conditions typical of KS are critical for KSHV sarcomagenesis. This is because growth in KS-like conditions generates a de-repressed KSHV epigenome allowing oncogenic KSHV gene expression in infected Pα(+)S MSCs. Furthermore, these growth conditions allow KSHV-infected Pα(+)S MSCs to overcome KSHV-driven oncogeneinduced senescence and cell cycle arrest via a PDGFRA-signaling mechanism; thus identifying PDGFRA not only as a phenotypic determinant for KS-progenitors but also as a critical enabler for viral oncogenesis.

Original languageEnglish (US)
Article numbere1008221
JournalPLoS pathogens
Volume15
Issue number12
DOIs
StatePublished - 2019

ASJC Scopus subject areas

  • Parasitology
  • Microbiology
  • Immunology
  • Molecular Biology
  • Genetics
  • Virology

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    Naipauer, J., Rosario, S., Gupta, S., Premer, C., Méndez-Solís, O., Schlesinger, M., Ponzinibbio, V., Jain, V., Gay, L., Renne, R., Chan, H. L., Morey, L., Salyakina, D., Abba, M., Williams, S., Hare, J. M., Goldschmidt-Clermont, P. J., & Mesri, E. A. (2019). PDGFRA defines the mesenchymal stem cell Kaposi's sarcoma progenitors by enabling KSHV oncogenesis in an angiogenic environment. PLoS pathogens, 15(12), [e1008221]. https://doi.org/10.1371/journal.ppat.1008221