Can thymic epithelial cells be infected by human T-lymphotropic virus type 1?

Moreira-Ramos, Klaysa; Castro, Flavia Madeira Monteiro de; Linhares-Lacerda, Leandra; Savino, Wilson

doi:10.1590/s0074-02762011000600018

Cited by 5 publications

(3 citation statements)

References 22 publications

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“…Then, HTLV-1-infected or non-infected T lymphocytes were added to the astrocyte monolayer at a ratio astrocyte: lymphocyte of 1:4 and allowed to adhere for 30 min at 37 °C, 5 % CO 2 in RPMI 1640 supplemented with 2 mM L-glutamine and antibiotics in absence of FCS and IL-2. Supernatants containing floating lymphocytes were then discarded and the contents of each flask (astrocytes + adhered lymphocytes) were fixed in absolute ethanol, stained with Giemsa and counted to determine the adhesion index (AI), as previously described [ 51 ] and validated for this type of analysis [ 52 ], using the following formula: …”

Section: Methodsmentioning

confidence: 99%

HAM/TSP-derived HTLV-1-infected T cell lines promote morphological and functional changes in human astrocytes cell lines: possible role in the enhanced T cells recruitment into Central Nervous System

Gudo

Silva-Barbosa

Linhares-Lacerda

et al. 2015

Virol J

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BackgroundThe mechanisms through which HTLV-1 leads to and maintains damage in the central nervous system of patients undergoing HTLV-1 associated myelopathy/tropical spastic paraparesis (HAM/TSP) are still poorly understood. In recent years, increasing evidence indicates that, not only lymphocytes but also glial cells, in particular astrocytes, play a role in the pathophysiology of HAM/TSP. In this study we used a model of co-culture between human HTLV-1-infected (CIB and C91PL) and non-infected (CEM) T lymphocyte cell lines and astrocyte (U251 and U87) cell lines to mimic the in vivo T cell-astrocyte interactions.ResultsWe first observed that CIB and C91PL adhere strongly to cultured astrocytes cell lines, and that co-cultures of HTLV-1 infected and astrocyte cell lines cells resulted in rapid syncytium formation, accompanied by severe morphological alterations and increased apoptotic cell death of astrocyte cells. Additionally, cultures of astrocyte cell lines in presence of supernatants harvested from HTLV-1-infected T cell cultures resulted in significant increase in the mRNA of CCL2, CXCL1, CXCL2, CXCL3, CXCL10, IL-13, IL-8, NFKB1, TLR4, TNF, MMP8 and VCAM1, as compared with the values obtained when we applied supernatants of non-infected T- cell lines. Lastly, soluble factors secreted by cultured astrocytic cell lines primed through 1-h interaction with infected T cell lines, further enhanced migratory responses, as compared to the effect seen when supernatants from astrocytic cell lines were primed with non-infected T cell lines.ConclusionCollectively, our results show that HTLV-1 infected T lymphocyte cell lines interact strongly with astrocyte cell lines, leading to astrocyte damage and increased secretion of attracting cytokines, which in turn may participate in the further attraction of HTLV-1-infected T cells into central nervous system (CNS), thus amplifying and prolonging the immune damage of CNS.Electronic supplementary materialThe online version of this article (doi:10.1186/s12985-015-0398-x) contains supplementary material, which is available to authorized users.

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Section: Methodsmentioning

confidence: 99%

HAM/TSP-derived HTLV-1-infected T cell lines promote morphological and functional changes in human astrocytes cell lines: possible role in the enhanced T cells recruitment into Central Nervous System

Gudo

Silva-Barbosa

Linhares-Lacerda

et al. 2015

Virol J

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“…Moreover, viral particles produced within TEC were infective. Interestingly, the human TEC line could also be infected with other RNA viruses, namely the retrovirus HTLV-1 15 . Moreover, pioneer work has shown that primary cultures of human TEC can also be infected with HIV 12 .…”

Section: Discussionmentioning

confidence: 99%

Zika virus targets the human thymic epithelium

Messias

Loss-Morais

Carvalho

et al. 2020

Sci Rep

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Previous work showed that the thymus can be infected by RNA viruses as HIV and HTLV-1. We thus hypothesized that the thymus might also be infected by the Zika virus (ZIKV). Herein we provide compelling evidence that ZIKV targets human thymic epithelial cells (TEC) in vivo and in vitro. ZIKVinfection enhances keratinization of TEC, with a decrease in proliferation and increase in cell death. Moreover, ZIKV modulates a high amount of coding RNAs with upregulation of genes related to cell adhesion and migration, as well as non-coding genes including miRNAs, circRNAs and lncRNAs. Moreover, we observed enhanced attachment of lymphoblastic T-cells to infected TEC, as well as virus transfer to those cells. Lastly, alterations in thymuses from babies congenitally infected were seen, with the presence of viral envelope protein in TEC. Taken together, our data reveals that the thymus, particularly the thymic epithelium, is a target for the ZIKV with changes in the expression of molecules that are relevant for interactions with developing thymocytes. Zika virus (ZIKV) epidemics in 2015-2016 resulted in devastating effects, causing microcephaly, other related congenital defects at birth and neurodevelopmental delay after two years in children born from mothers infected by the virus during pregnancy 1-4. Additionally, ZIKV infection in adults correlated with a rise in the frequency of cases of Guillain-Barré syndrome 5,6. Although the knowledge on the cellular and molecular alterations caused by the ZIKV in the nervous tissue largely increased in the last few years 2,7,8 , the effects of this virus upon hematopoietic tissues are much less defined. In terms of secondary lymphoid organs, ZIKV RNA and protein have been described in lymph nodes of Rhesus monkeys in both paracortex and germinal centers 9,10. The virus was also found in macrophages, dendritic cells, and B-cells, in both spleen and axillary lymph nodes of this non-human primate. However, in the same study, the presence of ZIKV RNA in T-cells was observed only in axillary lymph nodes from one animal 10. Much less is known on the putative infection of primary lymphoid organs, and more particularly in the thymus. This central lymphoid organ is responsible for the generation of T lymphocytes under the control of the thymic microenvironment, a three-dimensional cellular network mainly composed by thymic epithelial cells-TEC 11. In this respect, it is interesting to note the thymus as a target organ for other RNA viruses, such as HIV 12 and HTLV-1 13,14. In fact, we showed that cultured human TEC can be infected by HTLV-1 and convey virus particles to lymphoblastic T cells 15,16. We thus hypothesized that the thymic epithelium might also be infected by the Zika virus. Herein we provide compelling evidence that ZIKV targets human TEC both in vivo and in vitro. Data are provided showing that ZIKV-infection enhances keratinization of TEC, with a decrease in proliferation and increase in cell death. Moreover, in vitro data revealed that the virus could modulate a high amount ...

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“…94,95 It had been previously shown that breast epithelial cells can be infected with HTLV-1 by co-cultivating them with HTLV-1 producing T-cells and these infected epithelial cells can also infect other epithelial. 94,[96][97][98][99] Unfortunately, still there is no serious epidemiological studies were done to examine possible involvement of HTLV-1 in breast cancer. There are only 2 poorly designed studies have been reported so far in the literature that has come up with unconvincing negative data.…”

Section: Discussionmentioning

confidence: 99%

Differential effects of HTLV-1 Tax oncoprotein on the different estrogen-induced-ER α-mediated transcriptional activities

et al. 2016

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The activated estrogen (E2) receptor α (ERα) is a potent transcription factor that is involved in the activation of various genes by 2 different pathways; a classical and non-classical. In classical pathway, ERα binds directly to E2-responsive elements (EREs) located in the appropriate genes promoters and stimulates their transcription. However, in non-classical pathway, the ERα can indirectly bind with promoters and enhance their activity. For instance, ERα activates BRCA1 expression by interacting with jun/fos complex bound to the AP-1 site in BRCA1 promoter. Interference with the expression and/or functions of BRCA1, leads to high risk of breast or/and ovarian cancer. HTLV-1Tax was found to strongly inhibit BRCA1 expression by preventing the binding of E2-ERα complex to BRCA1 promoter. Here we examined Tax effect on ERα induced activation of genes by the classical pathway by testing its influence on E2-induced expression of ERE promoter-driven luciferase reporter (ERE-Luc). Our findings showed that E2 profoundly stimulated this reporter expression and that HTLV-1Tax significantly induced this stimulation. This result is highly interesting because in our previous study Tax was found to strongly block the E2-ERα-mediated activation of BRCA1 expression. ERα was found to produce a big complex by recruiting various cofactors in the nucleus before binding to the ERE region. We also found that only part of the reqruited cofactors are required for the transcriptional activity of ERα complex. Chip assay revealed that the binding of Tax to the ERα complex, did not interfere with its link to ERE region.

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Can thymic epithelial cells be infected by human T-lymphotropic virus type 1?

Abstract: The human

Cited by 5 publications

References 22 publications

HAM/TSP-derived HTLV-1-infected T cell lines promote morphological and functional changes in human astrocytes cell lines: possible role in the enhanced T cells recruitment into Central Nervous System

HAM/TSP-derived HTLV-1-infected T cell lines promote morphological and functional changes in human astrocytes cell lines: possible role in the enhanced T cells recruitment into Central Nervous System

Zika virus targets the human thymic epithelium

Differential effects of HTLV-1 Tax oncoprotein on the different estrogen-induced-ER α-mediated transcriptional activities

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