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Identifying Dysregulated Genes Induced by Kaposi's Sarcoma-associated Herpesvirus (KSHV)
07:02

Identifying Dysregulated Genes Induced by Kaposi's Sarcoma-associated Herpesvirus (KSHV)

Published on: September 14, 2010

Pivotal advance: Kaposi's sarcoma-associated herpesvirus (KSHV)-encoded microRNA specifically induce IL-6 and IL-10

Zhiqiang Qin1, Patricia Kearney, Karlie Plaisance

  • 1Department of Medicine, Hollings Cancer Center, Medical University of South Carolina,Charleston, South Carolina, USA.

Journal of Leukocyte Biology
|January 7, 2010
PubMed

Insights

Kaposi sarcoma-associated herpesvirus (KSHV) encoded microRNAs reprogram macrophages to secrete tumor-promoting cytokines like IL-6 and IL-10. This reprogramming involves targeting the C/EBPbeta transcription factor, driving KSHV-driven cancer progression.

Area of Science:

  • Immunology
  • Virology
  • Molecular Biology

Background:

  • Macrophages are key immune cells that can either fight or promote tumors.
  • In KSHV-associated cancers, macrophages may contribute to tumor growth by secreting specific cytokines.
  • The precise role of KSHV-infected macrophages in shaping the tumor microenvironment's cytokine profile remains unclear.

Purpose of the Study:

  • To investigate how KSHV-encoded microRNAs influence macrophage cytokine secretion.
  • To determine the molecular mechanisms by which KSHV miRNAs affect cytokine production in macrophages.
  • To elucidate the role of KSHV-driven macrophage reprogramming in KSHV-associated tumorigenesis.

Main Methods:

  • Utilized murine macrophages and human myelomonocytic cells to study KSHV miRNA effects.
  • Employed bioinformatics to identify miRNA binding sites on target genes.
  • Performed immunoblot analyses to assess protein expression changes.
  • Used RNA interference to validate the role of specific protein isoforms.

Main Results:

  • KSHV microRNAs (miRNAs) were found to induce secretion of IL-6 and IL-10 in macrophages.
  • Bioinformatics and immunoblotting revealed KSHV miRNAs target C/EBPbeta transcription factor, specifically reducing the inhibitory isoform LIP.
  • Targeting LIP directly led to increased IL-6 and IL-10 secretion by macrophages.

Conclusions:

  • KSHV miRNAs play a significant role in programming macrophage cytokine responses.
  • This reprogramming favors the secretion of pro-tumorigenic cytokines (IL-6, IL-10) by macrophages.
  • These findings highlight a mechanism by which KSHV promotes cancer progression through macrophage manipulation.

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