Tax Secretion From Peripheral Blood Mononuclear Cells and Tax Detection in Plasma of Patients With Human T-Lymphotropic Virus-Type 1-Associated Myelopathy/Tropical Spastic Paraparesis and Asymptomatic Carriers
Author
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Medina, Fernando
Author
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Quintremil, Sebastián
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Alberti, Carolina
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Godoy, Fabián
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Pando, María E.
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Bustamante, Andrés
Author
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Barriga, Andrés
Author
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Cartier Rovirosa, Luis
Author
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Puente Piccardo, Javier
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Tanaka, Yuetsu
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Valenzuela, Mar ía A.
Author
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Ramírez, Eugenio
Admission date
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2016-07-05T16:54:45Z
Available date
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2016-07-05T16:54:45Z
Publication date
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2016
Cita de ítem
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Journal of Medical Virology 88:521–531 (2016)
en_US
Identifier
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DOI 10.1002/jmv.24342
Identifier
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https://repositorio.uchile.cl/handle/2250/139422
General note
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Artículo de publicación ISI
en_US
Abstract
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Human T-lymphotropic virus-type 1 (HTLV-1) is the etiologic agent of the neurologic disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Tax viral protein plays a critical role in viral pathogenesis. Previous studies suggested that extracellular Tax might involve cytokine-like extracellular effects. We evaluated Tax secretion in 18 h-ex vivo peripheral blood mononuclear cells (PBMCs) cultures from 15 HAM/TSP patients and 15 asymptomatic carriers. Futhermore, Tax plasma level was evaluated from other 12 HAM/TSP patients and 10 asymptomatic carriers. Proviral load and mRNA encoding Tax were quantified by PCR and real-time RT-PCR, respectively. Intracellular Tax in CD4(+) CD25(+) cells occurred in 100% and 86.7% of HAM/TSP patients and asymptomatic carriers, respectively. Percentage of CD4(+) CD25(+) Tax+, proviral load and mRNA encoding Tax were significantly higher in HAM/TSP patients. Western blot analyses showed higher secretion levels of ubiquitinated Tax in HAM/TSP patients than in asymptomatic carriers. In HTLV-1-infected subjects, Western blot of plasma Tax showed higher levels in HAM/TSP patients than in asymptomatic carriers, whereas no Tax was found in noninfected subjects. Immunoprecipitated plasma Tax resolved on SDS-PAGE gave two major bands of 57 and 48 kDa allowing identification of Tax and Ubiquitin peptides by mass spectrometry. Relative percentage of either CD4(+) CD25(+) Tax+ cells, or Tax protein released from PBMCs, or plasma Tax, correlates neither with tax mRNA nor with proviral load. This fact could be explained by a complex regulation of Tax expression. Tax secreted from PBMCs or present in plasma could potentially become a biomarker to distinguish between HAM/TSP patients and asymptomatic carriers.
en_US
Patrocinador
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Fondecyt
1080396
Comision Nacional de Investigacion Cientifica y Tecnologica (Conicyt) from Chile
24090150
Tax Secretion From Peripheral Blood Mononuclear Cells and Tax Detection in Plasma of Patients With Human T-Lymphotropic Virus-Type 1-Associated Myelopathy/Tropical Spastic Paraparesis and Asymptomatic Carriers