Protein Profile of Blood Monocytes is Altered in HTLV-1 Infected Patients: Implications for HAM/TSP Disease

Juliana Echevarria-Lima,Russolina B Zingali,Marco Antonio Lima,Clarissa Rodrigues Nascimento,Thais Silva de Oliveira,Otávio de Melo Espíndola,Denise de Abreu Pereira,Vanessa Sandim,Ana Cláudia Celestino Leite,Dario E Kalume

doi:10.1038/s41598-018-32324-2

Abstract

Human T-cell lymphotropic virus type-1 (HTLV-1) is the etiological agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). The endothelial breakdown and migration of leukocytes, including monocytes, to the spinal cord are involved in HAM/TSP development. Monocytes from HTLV-1-infected individuals exhibit important functional differences when compared to cells from uninfected donors. Using proteomic shot gun strategy, performed by nanoACQUITY-UPLC system, we analyzed monocytes isolated from peripheral blood of asymptomatic carriers (AC), HAM/TSP and uninfected individuals. 534 proteins were identified among which 376 were quantified by ExpressionE software. Our study revealed a panel of changes in protein expression linked to HTLV-1 infection. Upregulation of heat shock proteins and downregulation of canonical histone expression were observed in monocytes from HTLV-1-infected patients. Moreover, expression of cytoskeleton proteins was increased in monocytes from HTLV-1-infected patients, mainly in those from HAM/TSP, which was confirmed by flow cytometry and fluorescence microscopy. Importantly, functional assays demonstrated that monocytes from HAM/TSP patients present higher ability for adhesion and transmigration thought endothelium than those from AC and uninfected individuals. The major changes on monocyte protein profile were detected in HAM/TSP patients, suggesting that these alterations exert a relevant role in the establishment of HAM/TSP.

Highlights

Human T-cell lymphotropic virus type-1 (HTLV-1) is the etiological agent of Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP)
Protein profile of pooled monocytes obtained from peripheral blood of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), asymptomatic carriers (AC) and uninfected individuals were submitted to tryptic digestion and were analyzed by LCMSE, in triplicates
Three replicates data sets were analyzed for each sample group, and prior to performing quantitative analysis. 159,490 exact mass retention time (EMRT) clusters were identified; among the replicate injections, the average coefficient of variation (CV) of the measured signal intensity was under 7% in all three samples

Summary

Introduction

Human T-cell lymphotropic virus type-1 (HTLV-1) is the etiological agent of HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Monocytes from HTLV-1-infected individuals exhibit important functional differences when compared to cells from uninfected donors. Functional assays demonstrated that monocytes from HAM/TSP patients present higher ability for adhesion and transmigration thought endothelium than those from AC and uninfected individuals. Human T-cell lymphotropic virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma (ATLL) malignancy[1] and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), a chronic progressive disabling disease characterized by demyelination, axonal loss, neuronal degeneration and gliosis[2]. Our group demonstrated that monocytes from HTLV-1-infected individuals, AC and HAM/TSP patients, presented reduced ability for in vitro differentiation into DCs when compared to monocytes from uninfected donors[22]. HTLV-1-infected cells have been described as exhibiting alterations in protein expression profiles, such as the reduction in choline, phosphocholine, spermine and glutathione production, and an increase in creatine, dopamine, arginine and adenosine monophosphate levels[23]

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