Institute for Frontier Life and Medical Sciences, Kyoto University

Sporadic on/off switching of HTLV-1 Tax expression is crucial to maintain the whole population of virus-induced leukemic cells

Mohamed Mahgoub1、Jun-ichirou Yasunaga1、Shingo Iwami2,3,4、Shinji Nakaoka3,5、Yoshiki Koizumi6、 Kazuya Shimura1、and Masao Matsuoka1,7

(1Laboratory of Virus Control, Institute for Frontier Life and Medical Sciences, Kyoto University; 2Mathematical Biology Laboratory, Department of Biology, Faculty of Sciences, Kyushu University; 3PRESTO, Japan Science and Technology Agency; 4CREST, Japan Science and Technology Agency; 5Institute of Industrial Sciences, The University of Tokyo; 6School of Medicine, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University; 7Department of Hematology, Rheumatology and Infectious Diseases, Kumamoto University School of Medicine

“Sporadic on/off switching of HTLV-1 Tax expression is crucial to maintain the whole population of virus-induced leukemic cells”

Proc Natl Acad Sci USA (2018) doi: 10.1073/pnas.1715724115

Abstract

Human T-cell leukemia virus type 1 (HTLV-1) establishes persistent infection in CD4+ T cells, and induces adult T-cell leukemia (ATL) after a long latent period. This study identified novel mechanisms of viral persistence regulated by a viral oncoprotein, Tax. Tax is a potent activator of viral replication and many signaling pathways involved in cancer development. Tax expression is generally suppressed in infected cells to evade host immune system. Therefore, its precise roles in pathogenesis remained unclear. This study shows that only a small subpopulation of HTLV-1-induced leukemic cells expresses Tax for a short span of time. This limited Tax expression is required to maintain the whole cell population through inhibition of cell death. Tax is induced by various stresses, suggesting that Tax efficiently protects cells from cell death and enhances virus production under stressful conditions. It is an elaborated strategy of HTLV-1 to evade host immunity and enable persistence in vivo.