Abstract
Human T-lymphotropic virus type 1 (HTLV-1) is a causative agent of adult T cell leukemia/lymphoma and a variety of inflammatory disorders. HTLV-1 encodes a nuclear localizing protein, p30, that selectively alters viral and cellular gene expression, activates G(2)-M cell cycle checkpoints, and is essential for viral spread. Here, we used immunoprecipitation and affinity pulldown of ectopically expressed p30 coupled with mass spectrometry to identify cellular binding partners of p30. Our data indicate that p30 specifically binds to cellular ATM (ataxia telangiectasia mutated) and REGγ (a nuclear 20 S proteasome activator). Under conditions of genotoxic stress, p30 expression was associated with reduced levels of ATM and increased cell survival. Knockdown or overexpression of REGγ paralleled p30 expression, suggesting an unexpected enhancement of p30 expression in the presence of REGγ. Finally, size exclusion chromatography revealed the presence of p30 in a high molecular mass complex along with ATM and REGγ. On the basis of our findings, we propose that HTLV-1 p30 interacts with ATM and REGγ to increase viral spread by facilitating cell survival.
Highlights
Human T-lymphotropic virus type 1 (HTLV-1)2 is a complex deltaretrovirus and the first reported human retrovirus linked to malignancy (1, 2)
On the basis of our findings, we propose that HTLV-1 p30 interacts with ATM and REG␥ to increase viral spread by facilitating cell survival
HTLV-1 p30 Promotes Cell Survival in the Presence of Genotoxic Stress—HTLV-1 infection is characterized by lymphocyte-mediated diseases, and the virus has well documented properties that promote the proliferation of infected cells through cell cycle alterations or cell signaling pathways (29, 30)
Summary
Human T-lymphotropic virus type 1 (HTLV-1)2 is a complex deltaretrovirus and the first reported human retrovirus linked to malignancy (1, 2). HTLV-1 encodes a nuclear localizing protein, p30, that selectively alters viral and cellular gene expression, activates G2-M cell cycle checkpoints, and is essential for viral spread. These studies support the role of p30 as a multifunctional protein with transcriptional and post-transcriptional activities that balance the influence of Tax to regulate viral gene expression and modulate host cell factors to promote survival of infected cells.
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