scholarly journals Noninvasive Detection of Antibodies to Human T-Cell Lymphotropic Virus Types 1 and 2 by Use of Oral Fluid

2019 ◽  
Vol 57 (12) ◽  
Author(s):  
Timothy Woo ◽  
Carolina Rosadas ◽  
Samreen Ijaz ◽  
Steve Dicks ◽  
Jennifer H. C. Tosswill ◽  
...  
Keyword(s):  
T Cell ◽  
Large Scale ◽  
Oral Fluid ◽  
Venous Blood ◽  
Spastic Paraparesis ◽  
Population Level ◽  
Field Testing ◽  
Igg Antibody ◽  
Serological Screening ◽  
Human T Cell

ABSTRACT Human T-lymphotropic viruses type 1 and 2 (HTLV-1/2) are prevalent in endemic clusters globally, and HTLV-1 infects at least 5 to 10 million individuals. Infection can lead to inflammation in the spinal cord, resulting in HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP), or adult T cell leukemia/lymphoma (ATL). Obtaining venous blood for serological screening, typically performed using enzyme immunoassays (EIAs), is invasive, sometimes socially unacceptable, and has restricted large-scale seroprevalence studies. Collecting oral fluid (OF) is a noninvasive alternative to venesection. In this study, an IgG antibody capture EIA was developed and validated to detect anti-HTLV-1/2 IgG in OF. OF and plasma specimens were obtained from seropositive HTLV-1/2-infected patients attending the National Centre for Human Retrovirology (n = 131) and from HTLV-1/2-uninfected individuals (n = 64). The assay showed good reproducibility and high diagnostic sensitivity (100%) and specificity (100%) using both OF and plasma. The Murex HTLV I+II commercial assay was evaluated and did not detect anti-HTLV-1/2 IgG in 14% (5/36) of OF specimens from seropositive donors. The reactivities of OF and plasma in the IgG capture correlated strongly (r = 0.9290) and were not significantly affected by delayed extraction when held between 3°C and 45°C for up to 7 days to simulate field testing. The use of OF serological screening for HTLV-1/2 infection could facilitate large-scale seroprevalence studies, enabling active surveillance of infection on a population level.

Human T-cell Lymphotropic Virus

2018 ◽  
Author(s):  
Hiroyuki Moriuchi
Keyword(s):  
T Cell ◽  
Inflammatory Diseases ◽  
Spastic Paraparesis ◽  
Central Africa ◽  
Perinatal Transmission ◽  
Serological Screening ◽  
Adult T Cell Leukemia ◽  
Human T Cell ◽  
West And Central Africa

Human T-cell lymphotropic virus type 1 (HTLV-1), a human retrovirus that infects an estimated 10–20 million people worldwide, has endemic foci in Japan, West and Central Africa, the Caribbean, Central and South America, and Melanesia. Also, it is the etiological agent of a lymphoproliferative malignancy, adult T-cell leukemia/lymphoma (ATLL), as well as chronic inflammatory diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 can be transmitted vertically, sexually, or by blood-borne transmission. ATLL occurs in approximately 5% of carriers who are infected during early childhood, and primary prevention is the only strategy likely to reduce this fatal disease. Children born to carrier mothers acquire the virus predominantly from breastfeeding. In endemic areas, mother-to-child transmission (MTCT) can be significantly reduced by screening pregnant women for the HTLV-1 antibody, followed by replacing breastfeeding with exclusive formula feeding. Indications for serological screening and recommendations for prevention of perinatal transmission are reviewed in this chapter.

scholarly journals Germinal epimutation of Fragile Histidine Triad (FHIT) gene is associated with progression to acute and chronic adult T-cell leukemia diseases

2021 ◽  
Vol 20 (1) ◽  
Author(s):  
Marcia Bellon ◽  
Izabela Bialuk ◽  
Veronica Galli ◽  
Xue-Tao Bai ◽  
Lourdes Farre ◽  
...  
Keyword(s):  
T Cell ◽  
Tumor Suppressor ◽  
Spastic Paraparesis ◽  
Cellular Transformation ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Fragile Histidine Triad ◽  
Adult T Cell Leukemia ◽  
Human T Cell

Abstract Background Human T cell Leukemia virus type 1 (HTLV-I) is etiologically linked to adult T cell leukemia/lymphoma (ATL) and an inflammatory neurodegenerative disease called HTLV-I-associated myelopathy or tropical spastic paraparesis (HAM/TSP). The exact genetic or epigenetic events and/or environmental factors that influence the development of ATL, or HAM/TSP diseases are largely unknown. The tumor suppressor gene, Fragile Histidine Triad Diadenosine Triphosphatase (FHIT), is frequently lost in cancer through epigenetic modifications and/or deletion. FHIT is a tumor suppressor acting as genome caretaker by regulating cellular DNA repair. Indeed, FHIT loss leads to replicative stress and accumulation of double DNA strand breaks. Therefore, loss of FHIT expression plays a key role in cellular transformation. Methods Here, we studied over 400 samples from HTLV-I-infected individuals with ATL, TSP/HAM, or asymptomatic carriers (AC) for FHIT loss and expression. We examined the epigenetic status of FHIT through methylation specific PCR and bisulfite sequencing; and correlated these results to FHIT expression in patient samples. Results We found that epigenetic alteration of FHIT is specifically found in chronic and acute ATL but is absent in asymptomatic HTLV-I carriers and TSP/HAM patients’ samples. Furthermore, the extent of FHIT methylation in ATL patients was quantitatively comparable in virus-infected and virus non-infected cells. We also found that longitudinal HTLV-I carriers that progressed to smoldering ATL and descendants of ATL patients harbor FHIT methylation. Conclusions These results suggest that germinal epigenetic mutation of FHIT represents a preexisting mark predisposing to the development of ATL diseases. These findings have important clinical implications as patients with acute ATL are rarely cured. Our study suggests an alternative strategy to the current “wait and see approach” in that early screening of HTLV-I-infected individuals for germinal epimutation of FHIT and early treatment may offer significant clinical benefits.

scholarly journals A primary human T-cell spectral library to facilitate large scale quantitative T-cell proteomics

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Harshi Weerakoon ◽  
Jeremy Potriquet ◽  
Alok K. Shah ◽  
Sarah Reed ◽  
Buddhika Jayakody ◽  
...  
Keyword(s):  
T Cell ◽  
Large Scale ◽  
Large Data ◽  
Spectral Library ◽  
Proteomics Data ◽  
Cell Library ◽  
Public Resource ◽  
Human T Cell ◽  
Theoretical Mass ◽  
Current Resource

AbstractData independent analysis (DIA) exemplified by sequential window acquisition of all theoretical mass spectra (SWATH-MS) provides robust quantitative proteomics data, but the lack of a public primary human T-cell spectral library is a current resource gap. Here, we report the generation of a high-quality spectral library containing data for 4,833 distinct proteins from human T-cells across genetically unrelated donors, covering ~24% proteins of the UniProt/SwissProt reviewed human proteome. SWATH-MS analysis of 18 primary T-cell samples using the new human T-cell spectral library reliably identified and quantified 2,850 proteins at 1% false discovery rate (FDR). In comparison, the larger Pan-human spectral library identified and quantified 2,794 T-cell proteins in the same dataset. As the libraries identified an overlapping set of proteins, combining the two libraries resulted in quantification of 4,078 human T-cell proteins. Collectively, this large data archive will be a useful public resource for human T-cell proteomic studies. The human T-cell library is available at SWATHAtlas and the data are available via ProteomeXchange (PXD019446 and PXD019542) and PeptideAtlas (PASS01587).

scholarly journals Cytokine Networks Dysregulation during HTLV-1 Infection and Associated Diseases

Viruses ◽  
2018 ◽  
Vol 10 (12) ◽  
pp. 691 ◽  
Author(s):  
Nicolas Futsch ◽  
Gabriela Prates ◽  
Renaud Mahieux ◽  
Jorge Casseb ◽  
Hélène Dutartre
Keyword(s):  
T Cell ◽  
Immune Escape ◽  
Leukemia Virus ◽  
Spastic Paraparesis ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Associated Diseases ◽  
Cytokines And Chemokines ◽  
Human T Cell

Human T-cell leukemia virus type 1 (HTLV-1) is the causative agent of a neural chronic inflammation, called HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and of a malignant lymphoproliferation, called the adult T-cell leukemia/lymphoma (ATLL). The mechanisms through which the HTLV-1 induces these diseases are still unclear, but they might rely on immune alterations. HAM/TSP is associated with an impaired production of pro-inflammatory cytokines and chemokines, such as IFN-γ, TNF-α, CXCL9, or CXCL10. ATLL is associated with high levels of IL-10 and TGF-β. These immunosuppressive cytokines could promote a protumoral micro-environment. Moreover, HTLV-1 infection impairs the IFN-I production and signaling, and favors the IL-2, IL-4, and IL-6 expression. This contributes both to immune escape and to infected cells proliferation. Here, we review the landscape of cytokine dysregulations induced by HTLV-1 infection and the role of these cytokines in the HTLV-1-associated diseases progression.

scholarly journals Enhanced MDR1 Gene Expression in Human T-Cell Leukemia Virus-I–Infected Patients Offers New Prospects for Therapy

Blood ◽  
1998 ◽  
Vol 91 (7) ◽  
pp. 2467-2474 ◽  
Author(s):  
Alan Lau ◽  
Simon Nightingale ◽  
Graham P. Taylor ◽  
Timothy W. Gant ◽  
Alan J. Cann
Keyword(s):  
Drug Resistance ◽  
T Cell ◽  
Multiple Drug Resistance ◽  
Leukemia Virus ◽  
Spastic Paraparesis ◽  
Leukemic Cells ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Human T Cell ◽  
T Cell Leukemia Virus

Overexpression of P-glycoprotein (P-gp), the protein product of the multidrug resistance gene (MDR1), confers a drug resistant phenotype on cells. This phenotype is reminiscent of human T-cell leukemia virus (HTLV)-transformed leukemic cells, for which no consistently effective chemotherapeutic regime has been found. The presence of an active multiple drug resistance (MDR) phenotype in freshly isolated peripheral blood mononuclear cells (PBMC) from HTLV-I–infected subjects was investigated. Significant P-gp–mediated efflux activity and enhanced MDR1 mRNA expression was observed in nine of 10 HTLV-infected subjects. The development of MDR phenotypes was found to be independent of disease type or status with significant MDR activities being observed in adult T-cell leukemia (ATL), HTLV-associated myelopathy (HAM)/tropical spastic paraparesis (TSP), and asymptomatic HTLV-infected individuals. P-gp–mediated drug efflux was also found to be restricted to CD3+ T-cell populations. Furthermore, we show the novel finding that theMDR1 gene promoter is transcriptionally activated by the HTLV-I tax protein, suggesting a molecular basis for the development of drug resistance in HTLV-I infections. These observations open up the possibility of new chemotherapeutic approaches to HTLV-associated diseases through the use of P-gp inhibitors.

scholarly journals HIV-1 and HTLV-1 Transmission Modes: Mechanisms and Importance for Virus Spread

Viruses ◽  
2022 ◽  
Vol 14 (1) ◽  
pp. 152
Author(s):  
Svetlana Kalinichenko ◽  
Dmitriy Komkov ◽  
Dmitriy Mazurov
Keyword(s):  
T Cell ◽  
Spastic Paraparesis ◽  
Latency Period ◽  
Autoimmune Disorder ◽  
Adult T Cell Leukemia ◽  
Modes Of Transmission ◽  
Human T Cell ◽  
Immunodeficiency Syndrome ◽  
Hiv 1

So far, only two retroviruses, human immunodeficiency virus (HIV) (type 1 and 2) and human T-cell lymphotropic virus type 1 (HTLV-1), have been recognized as pathogenic for humans. Both viruses mainly infect CD4+ T lymphocytes. HIV replication induces the apoptosis of CD4 lymphocytes, leading to the development of acquired immunodeficiency syndrome (AIDS). After a long clinical latency period, HTLV-1 can transform lymphocytes, with subsequent uncontrolled proliferation and the manifestation of a disease called adult T-cell leukemia (ATLL). Certain infected patients develop neurological autoimmune disorder called HTLV-1-associated myelopathy, also known as tropical spastic paraparesis (HAM/TSP). Both viruses are transmitted between individuals via blood transfusion, tissue/organ transplantation, breastfeeding, and sexual intercourse. Within the host, these viruses can spread utilizing either cell-free or cell-to-cell modes of transmission. In this review, we discuss the mechanisms and importance of each mode of transmission for the biology of HIV-1 and HTLV-1.

Analyzing Interval Systems of Human T-Cell Lymphotropic Virus Type I Infection of CD4+ T-Cells

2017 ◽  
pp. 126-147
Author(s):  
Zohreh Dadi
Keyword(s):  
T Cell ◽  
Virus Type ◽  
Lupus Erythematosus ◽  
Dynamical Behavior ◽  
Spastic Paraparesis ◽  
Type I ◽  
Cell Dynamics ◽  
Adult T Cell Leukemia ◽  
Human T Cell ◽  
Study Interval

Human T-cell lymphotropic virus type I (HTLV-I) infects a type of white blood cell called a T lymphocyte. HTLV-I infection is seen in diverse region of the world such as the Caribbean Islands, southwestern Japan, southeastern United States, and Mashhad (Iran). This virus is the etiological agent of two main types of disease: HTLV-I-associated myelopathy/tropical spastic paraparesis and adult T cell leukemia. Also, the role of HTLV-I in the pathogenesis of autoimmune diseases such as HTLV-I associated arthropathy and systemic lupus erythematosus is under investigation. In this chapter, the author considers an ODE model of T-cell dynamics in HTLV-I infection which was proposed by Stilianakis and Seydel in 1999. Mathematical analysis of the model with fixed parameters has been done by many researchers. The author studies dynamical behavior (local stability) of this model with interval uncertainties, called interval system. Also, effective parameters in the local dynamics of model are found. For this study, interval analysis and particularly of Kharitonov's stability theorem are used.

scholarly journals HTLV-1 infection of myeloid cells: from transmission to immune alterations

Retrovirology ◽  
2019 ◽  
Vol 16 (1) ◽  
Author(s):  
Brenda Rocamonde ◽  
Auriane Carcone ◽  
Renaud Mahieux ◽  
Hélène Dutartre
Keyword(s):  
T Cell ◽  
Leukemia Virus ◽  
Spastic Paraparesis ◽  
Myeloid Cells ◽  
Cell Types ◽  
T Cell Leukemia ◽  
Cell Leukemia ◽  
Cell Leukemia Virus Type ◽  
Adult T Cell Leukemia ◽  
Human T Cell

AbstractHuman T cell leukemia virus type 1 (HTLV-1), the etiological agent of adult T-cell leukemia/lymphoma (ATLL) and the demyelinating neuroinflammatory disease known as HTLV-1-Associated Myelopathy/Tropical Spastic Paraparesis (HAM/TSP), was the first human retrovirus to be discovered. T-cells, which represent the main reservoir for HTLV-1, have been the main focus of studies aimed at understanding viral transmission and disease progression. However, other cell types such as myeloid cells are also target of HTLV-1 infection and display functional alterations as a consequence. In this work, we review the current investigations that shed light on infection, transmission and functional alterations subsequent to HTLV-1 infection of the different myeloid cells types, and we highlight the lack of knowledge in this regard.

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