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

Echevarria-Lima, Juliana; Pereira, Denise de Abreu; Oliveira, Thais Silva de; Espíndola, Otávio de Melo; Lima, Marco Antônio; Leite, Ana Cláudia Celestino Bezerra; Sandim, Vanessa; Nascimento, Christine Rabello; Kalume, Dário Eluan; Zingali, Russolina B.

doi:10.1038/s41598-018-32324-2

Cited by 4 publications

(10 citation statements)

References 60 publications

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“…Enose-Akahata et al (2012) observed the presence of phagocytes expressing high levels of HLA-DR and CX3CR1 in spinal cord injuries of individuals with HAM/TSP [21]. Using proteomic analysis, our group revealed important changes in the expression of cytoskeletal proteins in monocytes of HTLV-1 carriers, demonstrating an increase in proteins associated with adhesion and migration phenomena, such as gelsolin [17].…”

Section: Introductionmentioning

confidence: 72%

HTLV-1-infected cells drive the differentiation of monocytes into macrophages in vitro

Souza,

Melo,

Calôba

et al. 2024

Preprint

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Background. The human T-cell lymphotropic virus type 1 (HTLV-1) is a retrovirus that causes HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HAM/TSP is a chronic inflammatory neurodegenerative disease characterized by leukocyte infiltration in the spinal cord. T-lymphocytes are the most important targets of HTLV-1 infection, but monocytes are also infected. Monocytes from HTLV-1-infected individuals exhibit important functional differences compared to cells from uninfected donors. Here, we investigated the effects of cell-cell physical contact and/or secreted factors of HTLV-1-infected cells in monocyte activation and differentiation. Methods. The THP-1 human monocytic cell line was co-cultured with a human cell line transformed by HTLV-1 (MT-2) for 6 days. To determine the effects of co-culturing HTLV-1-infected cells in THP-1 monocytes cells were characterized by flow cytometry, immunofluorescence microscopy, and real-time PCR. Computational analysis of published transcriptomic datasets was realized to investigate molecular profiles of macrophages with mononuclear cells from HTLV-1 carriers. Results. Co-culture of monocytes with HTLV-1-infected cells induced macrophage differentiation and upregulation of typical macrophages-associated molecules (HLA-DR, CD80, and CD86), increased cytokine (TNFα, IL-6, and IL-1β) levels and their coding genes. Consistently, published transcriptomic datasets showed changes in important genes associated with inflammation during HAM/TSP in patients. The presence of HTLV-1-infected cells in the culture also induced significant upregulation of Interferon Stimulated Genes (ISG), indicating viral infection. Monocyte activation and differentiation into pro-inflammatory macrophages occurred in a cell-to-cell contact-independent manner, suggesting the role of factors secreted by infected cells. Conclusions. Together our results indicated that the presence of HTLV-1-infected cells can induce monocyte differentiation into macrophages, predominantly, inflammatory.

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Section: Introductionmentioning

confidence: 72%

HTLV-1-infected cells drive the differentiation of monocytes into macrophages in vitro

Souza,

Melo,

Calôba

et al. 2024

Preprint

Self Cite

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“…Heat shock proteins and cytoskeleton proteins were found to be upregulated, while canonical histones were downregulated in monocytes of HTLV-1-infected individuals. 9 However, there is no study available in the literature using the same markers as we used in the present study.…”

Section: Discussionmentioning

confidence: 99%

“…Several studies have shown that HTLV-1 infection leads to changes in the levels of some proteins. 1,9,10 Therefore, this study was conducted to evaluate some biomarkers (haematological, biochemical, and serological) in an HTLV-1-positive donor, which could be used for early HTLV-1 detection.…”

Section: 8mentioning

confidence: 99%

Changes in Serum Protein and Enzyme Levels in Human T Lymphotropic Virus-1-Infected Patient

Almaiman

2020

J Coll Physicians Surg Pak

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This study aims to evaluate the changes in serum protein levels in a patient with confirmed human T lymphotropic virus type-1 (HTLV-1) infection. Screening and confirmation tests were performed for HTLV-1, along with an assessment of overall albumin, alpha 1 and 2, and gamma and beta globulin levels, using SAS-3 protein electrophoretic analysis. HTLV-1 positivity was confirmed with enzyme-linked immunosorbent assay (ELISA) and nucleic acid amplification testing (NAT). The biochemical tests or protein levels did not exhibit any changes in HTLV-1 infection, indicating that HTLV-1 results in a rare silent infection that does not result in changes in protein levels at the early stages. To aid early detection of the virus and initiate treatment, a comprehensive investigation at the protein and gene levels should be performed.

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“…Thus, the regulation of HAX‐1 stability may be one of the pathways used by HBZ to block apoptosis. Another study demonstrated that monocytes isolated from HAM/TSP patients exhibit higher ability for adhesion and transmigration via endothelium than those isolated from asymptomatic carriers and uninfected individuals (Echevarria‐Lima et al, 2018). It has also been shown that HBZ resides exclusively in the cytoplasm of infected‐cells in asymptomatic carriers and HAM/TSP patients (Forlani et al, 2019).…”

Section: Discussionmentioning

confidence: 99%

HTLV‐1 viral oncoprotein HBZ contributes to the enhancement of HAX‐1 stability by impairing the ubiquitination pathway

Tanaka

Mukai

Ohshima

2020

Journal Cellular Physiology

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Human T‐cell leukemia virus type 1 (HTLV‐1) is an oncogenic retrovirus that causes adult T‐cell leukemia (ATL). The viral protein HTLV‐1 basic leucine‐zipper factor (HBZ), which is constitutively expressed in all ATL patient cells, contributes toward the development of ATL; however, the underlying mechanism has not been elucidated yet. Here, we identified HS‐1‐associated protein X‐1 (HAX‐1) as a novel binding partner of HBZ. Interestingly, HAX‐1 specifically associated with HBZ‐US, but not HBZ‐SI, in the cytoplasm. HBZ suppressed the polyubiquitination levels of HAX‐1 protein by inhibiting the association HAX‐1 with F‐box protein 25 (FBXO25), which is a member of the SCF E3 ubiquitin ligase complex, and promoted the stabilization of HAX‐1 levels. In fact, the protein levels of HAX‐1 were significantly increased in HTLV‐1 infected and the overexpressing HBZ in uninfected T‐cell lines. Enhanced HAX‐1 correlated well to suppression of caspase 9 processing, suggesting that HBZ may contribute to the enhancement of antiapoptotic function for HAX‐1. Our results revealed a role for HBZ on HAX‐1 stabilization by abrogating the ubiquitination‐mediated degradation pathway, which may play an important role in understanding the potential mechanisms of HTLV‐1 related pathogenesis.

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

Cited by 4 publications

References 60 publications

HTLV-1-infected cells drive the differentiation of monocytes into macrophages in vitro

HTLV-1-infected cells drive the differentiation of monocytes into macrophages in vitro

Changes in Serum Protein and Enzyme Levels in Human T Lymphotropic Virus-1-Infected Patient

HTLV‐1 viral oncoprotein HBZ contributes to the enhancement of HAX‐1 stability by impairing the ubiquitination pathway

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