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Updated: May 27, 2026
Identifying Dysregulated Genes Induced by Kaposi's Sarcoma-associated Herpesvirus (KSHV)
Published on: September 14, 2010
Viral microRNA targetome of KSHV-infected primary effusion lymphoma cell lines
Eva Gottwein1, David L Corcoran, Neelanjan Mukherjee
1Department of Microbiology-Immunology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA. e-gottwein@northwestern.edu
Abstract:
Primary effusion lymphoma (PEL) is caused by Kaposi's sarcoma-associated herpesvirus (KSHV) and frequently also harbors Epstein-Barr virus (EBV). The expression of KSHV- and EBV-encoded microRNAs (miRNAs) in PELs suggests a role for these miRNAs in latency and lymphomagenesis. Using PAR-CLIP, a technology which allows the direct and transcriptome-wide identification of miRNA targets, we delineate the target sites for all viral and cellular miRNAs expressed in PEL cell lines. The resulting data set revealed that KSHV miRNAs directly target more than 2000 cellular mRNAs, including many involved in pathways relevant to KSHV pathogenesis. Moreover, 58% of these mRNAs are also targeted by EBV miRNAs, via distinct binding sites. In addition to a known viral analog of cellular miR-155, we show that KSHV encodes a viral miRNA that mimics cellular miR-142-3p function. In summary, this study identifies an extensive list of KSHV miRNA targets, which are likely to influence viral replication and pathogenesis.
Insights
Kaposi's sarcoma-associated herpesvirus (KSHV) and Epstein-Barr virus (EBV) microRNAs target thousands of cellular genes in primary effusion lymphoma (PEL). These viral microRNAs play a significant role in KSHV pathogenesis and viral replication.
Area of Science:
- Oncology
- Virology
- Molecular Biology
Background:
- Primary effusion lymphoma (PEL) is a B-cell malignancy associated with Kaposi's sarcoma-associated herpesvirus (KSHV) and frequently Epstein-Barr virus (EBV).
- Viral microRNAs (miRNAs) expressed by KSHV and EBV are implicated in the latency and development of PEL.
Purpose of the Study:
- To comprehensively identify direct targets of all viral and cellular miRNAs expressed in PEL cell lines using a transcriptome-wide approach.
- To investigate the overlap and distinct binding sites of KSHV and EBV miRNA targets in PEL cells.
- To characterize novel viral miRNAs encoded by KSHV and their functional mimicry of cellular miRNAs.
Main Methods:
- Photoactivatable-Ribonucleoside-Enhanced Crosslinking and Immunoprecipitation (PAR-CLIP) technology was employed for direct and transcriptome-wide identification of miRNA targets.
- Analysis of miRNA target sites for both viral (KSHV, EBV) and cellular miRNAs within PEL cell lines.
- Functional characterization of KSHV-encoded miRNAs, including comparison with cellular miRNA functions.
Main Results:
- KSHV miRNAs were found to directly target over 2000 cellular messenger RNAs (mRNAs), impacting pathways crucial for KSHV pathogenesis.
- A significant overlap (58%) was observed where cellular mRNAs are targeted by both KSHV and EBV miRNAs, utilizing distinct binding sites.
- KSHV encodes a novel viral miRNA that functionally mimics the cellular miR-142-3p, in addition to a known viral analog of miR-155.
Conclusions:
- This study provides an extensive catalog of KSHV miRNA targets, offering insights into their roles in viral replication and lymphomagenesis.
- The findings highlight the complex interplay between viral and cellular miRNAs in PEL, mediated by extensive targeting of host cell pathways.
- The identification of novel viral miRNA functions underscores their importance in KSHV pathogenesis.
