A role for MALT1 activity in Kaposi's sarcoma-associated herpes virus latency and growth of primary effusion lymphoma
Bonsignore L, Passelli K, Pelzer C, Perroud M, Konrad A, Thurau M, Stürzl M, Dai L, Trillo-Tinoco J, Del Valle L, Qin Z, Thome M (2017)
Publication Type: Journal article
Publication year: 2017
Journal
Book Volume: 31
Pages Range: 614-624
Journal Issue: 3
DOI: 10.1038/leu.2016.239
Abstract
Primary effusion lymphoma (PEL) is an incurable malignancy that develops in immunodeficient patients as a consequence of latent infection of B-cells with Kaposi's sarcoma-associated herpes virus (KSHV). Malignant growth of KSHV-infected B cells requires the activity of the transcription factor nuclear factor (NF)-?B, which controls maintenance of viral latency and suppression of the viral lytic program. Here we show that the KSHV proteins K13 and K15 promote NF-?B activation via the protease mucosa-associated lymphoid tissue lymphoma translocation protein-1 (MALT1), a key driver of NF-?B activation in lymphocytes. Inhibition of the MALT1 protease activity induced a switch from the latent to the lytic stage of viral infection, and led to reduced growth and survival of PEL cell lines in vitro and in a xenograft model. These results demonstrate a key role for the proteolytic activity of MALT1 in PEL, and provide a rationale for the pharmacological targeting of MALT1 in PEL therapy.
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Switzerland (CH)
United States (USA) (US)How to cite
APA:
Bonsignore, L., Passelli, K., Pelzer, C., Perroud, M., Konrad, A., Thurau, M.,... Thome, M. (2017). A role for MALT1 activity in Kaposi's sarcoma-associated herpes virus latency and growth of primary effusion lymphoma. Leukemia, 31(3), 614-624. https://doi.org/10.1038/leu.2016.239
MLA:
Bonsignore, L., et al. "A role for MALT1 activity in Kaposi's sarcoma-associated herpes virus latency and growth of primary effusion lymphoma." Leukemia 31.3 (2017): 614-624.
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