Research Papers:

Viral oncomiR spreading between B and T cells is employed by Kaposi's sarcoma herpesvirus to induce non-cell-autonomous target gene regulation

Nir Rainy _, Morad Zayoud, Yoel Kloog, Oded Rechavi and Itamar Goldstein

PDF  |  HTML  |  Supplementary Files  |  How to cite  |  Order a Reprint

Oncotarget. 2016; 7:41870-41884. https://doi.org/10.18632/oncotarget.9627

Metrics: PDF 638 views  |   HTML 1039 views  |   ?  


Nir Rainy1,2,3, Morad Zayoud1,2, Yoel Kloog3, Oded Rechavi3, Itamar Goldstein1,2

1Sheba Cancer Research Center, Chaim Sheba Academic Medical Center, Tel Hashomer, Ramat Gan 5262100, Israel

2Sackler School of Medicine, Tel-Aviv University, Tel-Aviv 6997801, Israel

3Department of Neurobiology, The George S. Wise Faculty of Life Sciences & Sagol School of Neuroscience, Tel-Aviv University, Tel-Aviv 6997801, Israel

Correspondence to:

Itamar Goldstein, email: Itamar.Goldstein@sheba.health.gov.il

Keywords: microRNAs, herpesviruses, lymphoma, oncomiRs, viral carcinogenesis

Received: November 08, 2015     Accepted: May 08, 2016     Published: May 26, 2016


The two human lymphotrophic γ-herpesviruses, Kaposi's sarcoma herpesvirus (KSHV) and Epstein-Barr virus (EBV), are a recognized cause of human cancer, encoding multiple miRs that are major players in carcinogenesis. Previously, we discovered that EBV-encoded miRs transfer between infected B and T lymphocytes. To further explore the biological significance of the spreading of γ-herpesvirus-encoded miRs on carcinogenesis, we focused on KSHV-miR-K12-11 (miR-K12-11) that is unique in having an identical seed sequence with the oncomiR hsa-miR-155, implicated in B cell lymphomas development. Here, we show for the first time that miR-K12-11 transfers in vitro from KSHV-infected BCBL-1 and BC-1 lymphoma lines to T cells. The transferred miR-K12-11 is active in the adopting T cells and binds its canonical target, the 3’-UTR of BACH1. Importantly, we show that the transfer of miR-K12-11 from BCBL-1 to Jurkat cells correlates with inhibition of the innate type-I interferons response to viral dsRNAs downstream of IKKε, a validated miR-K12-11 target. Finally, we show that miR-K12-11 spreading is not reduced by blocking the classical ceramide-dependent exosome secretion pathway. In summary, we report for the first time that intercellular viral oncomiR spreading is an additional mechanism employed by KSHV to inhibit host anti-viral immunity and consequently promote oncogenesis.

Creative Commons License All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.
PII: 9627