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Ago HITS-CLIP expands understanding of Kaposi's sarcoma-associated herpesvirus miRNA function in primary effusion

Irina Haecker1, Lauren A Gay, Yajie Yang

  • 1Department of Molecular Genetics and Microbiology, University of Florida, Gainesville, Florida, United States of America.

Plos Pathogens
|August 29, 2012
PubMed

Insights

This study identifies numerous cellular and viral microRNA targets in Kaposi's sarcoma-associated herpesvirus (KSHV)-infected cells, revealing their crucial roles in viral pathogenesis and tumor development.

Area of Science:

  • Virology
  • Molecular Biology
  • Oncology

Background:

  • Kaposi's sarcoma-associated herpesvirus (KSHV) causes Kaposi's sarcoma (KS), primary effusion lymphoma (PEL), and multicentric Castleman's disease (MCD).
  • KSHV-encoded microRNAs (miRNAs) are found in tumors, suggesting a role in KSHV pathogenesis and tumorigenesis.
  • Understanding KSHV miRNA function requires identifying their cellular and viral targets.

Purpose of the Study:

  • To globally identify KSHV miRNA targets in latently infected PEL cell lines using Ago HITS-CLIP.
  • To investigate the role of KSHV miRNAs in viral pathogenesis and tumorigenesis.

Main Methods:

  • Performed Ago HITS-CLIP (High-Throughput Sequencing of RNA isolated by Crosslinking Immunoprecipitation) in two latently KSHV-infected PEL cell lines (BCBL-1 and BC-3).
  • Analyzed viral and cellular miRNA targets, focusing on seed matches in 3'UTRs.

Main Results:

  • Identified 1170 and 950 cellular KSHV miRNA targets in BCBL-1 and BC-3 cells, respectively.
  • Enriched targets included genes involved in apoptosis, cell cycle regulation, lymphocyte proliferation, and immune evasion.
  • Discovered high levels of KSHV miRNAs in BC-3 cells, suggesting potential hijacking of RISC complexes and global de-repression of cellular gene expression.

Conclusions:

  • Provides an extensive resource of KSHV miRNA targets, crucial for deciphering KSHV miRNA function.
  • KSHV miRNAs play significant roles in viral pathogenesis and potentially tumorigenesis by regulating key cellular pathways.
  • KSHV miRNAs may also contribute to disease by globally altering cellular gene expression through RISC complex modulation.

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