Combination of arsenic and interferon-α inhibits expression of KSHV latent transcripts and synergistically improves survival of mice with primary effusion lymphomas.

<h4>Background</h4>Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent of primary effusion lymphomas (PEL). PEL cell lines infected with KSHV, but negative for Epstein-Barr virus have a tumorigenic potential in non-obese diabetic/severe combined immunodeficient mice and r...

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Auteurs principaux: Hiba El Hajj, Jihane Ali, Akram Ghantous, Dana Hodroj, Ahmad Daher, Kazem Zibara, Chloé Journo, Zaher Otrock, Ghazi Zaatari, Renaud Mahieux, Marwan El Sabban, Ali Bazarbachi, Raghida Abou Merhi
Format: article
Langue:EN
Publié: Public Library of Science (PLoS) 2013
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R
Q
Accès en ligne:https://doaj.org/article/82a3ce35772b42f6be4136d67223f89e
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Résumé:<h4>Background</h4>Kaposi sarcoma-associated herpesvirus (KSHV) is the etiologic agent of primary effusion lymphomas (PEL). PEL cell lines infected with KSHV, but negative for Epstein-Barr virus have a tumorigenic potential in non-obese diabetic/severe combined immunodeficient mice and result in efficient engraftment and formation of malignant ascites with notable abdominal distension, consistent with the clinical manifestations of PEL in humans.<h4>Methodology/principal findings</h4>Using this preclinical mouse model, we demonstrate that the combination of arsenic trioxide and interferon-alpha (IFN) inhibits proliferation, induces apoptosis and downregulates the latent viral transcripts LANA-1, v-FLIP and v-Cyc in PEL cells derived from malignant ascites. Furthermore, this combination decreases the peritoneal volume and synergistically increases survival of PEL mice.<h4>Conclusion/significance</h4>These results provide a promising rationale for the therapeutic use of arsenic/IFN in PEL patients.