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Health Expectations : An International... Dec 2023Human T-cell lymphotropic virus type 1 (HTLV-1) is a chronic infection affecting 5-10 million people worldwide. Ten percent develop HTLV-1-associated diseases, and 3%-5%...
INTRODUCTION
Human T-cell lymphotropic virus type 1 (HTLV-1) is a chronic infection affecting 5-10 million people worldwide. Ten percent develop HTLV-1-associated diseases, and 3%-5% develop HTLV-1-associated myelopathy (HAM)/tropical spastic paraparesis. Low health-related quality of life (HRQoL) is a significant concern for those with HTLV-1, and little is known about how it impacts daily life or what patients need from healthcare services. To address this, we report on patient involvement workshops aimed at identifying research priorities for HTLV-1 health service provision.
METHODS
Participants recruited through HTLV-1 clinics in England attended six 90-min virtual workshops over 10 months, and two 60-min consolidation workshops. Content developed iteratively from topic focussed group discussions. All workshops were video-recorded with consent, transcribed verbatim and thematically analysed. Using consensus voting rounds, participants individually ranked their top six and then collectively their top three research priorities from the themes inferred from the analysis. A final feedback session explored the experiences of participating in the workshops.
FINDINGS
Twenty-seven people with HTLV-1 engaged with the workshops with up to 22 participants attending each meeting. The majority were diagnosed with HAM (n = 22). The top three research priorities were identified as understanding disease progression, psychosocial wellbeing, and information and knowledge. Participants valued being asked to set research priorities that directly addressed their needs and enjoyed the workshops. They stressed the importance of patient advocates for promoting research that positively impacts everyday life.
CONCLUSION
This is the first of this type of research engagement with people with HTLV-1 in the United Kingdom. Participants identified several avenues of investigation that could lead to improvements in healthcare services and HRQoL. Participants believed the workshops signified the start of a conversation to progress person-centred and meaningful research in HTLV-1.
PATIENT OR PUBLIC CONTRIBUTION
People living with HTLV-1 were involved in the iterative design, conduct, analysis, writing and dissemination of this project through the patient involvement workshops. As a result of this engagement, a patient led advisory group has been set up to assist with the dissemination of the findings.
Topics: Humans; Human T-lymphotropic virus 1; Quality of Life; Paraparesis, Tropical Spastic; Research; T-Lymphocytes
PubMed: 37578191
DOI: 10.1111/hex.13848 -
International Journal of Infectious... Aug 2024Infective dermatitis associated with human T-cell lymphotropic virus type-1 (HTLV-1) (IDH) is a severe form of chronically infected eczema occurring in early childhood,... (Review)
Review
Infective dermatitis associated with human T-cell lymphotropic virus type-1 (HTLV-1) (IDH) is a severe form of chronically infected eczema occurring in early childhood, although very rarely cases have been reported in adults. Most of the cases are from Jamaica and Brazil and occur in individuals with low socioeconomic status. IDH is always associated with refractory Staphylococcus aureus or beta-hemolytic Streptococcus infection of the skin and nasal vestibules. Patients with IDH may develop other even more severe HTLV-1-associated diseases, such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) of early or late appearance and adult T-cell leukemia/lymphoma. In the context of the Brazilian experience, it has been observed that 54% of IDH patients exhibit the juvenile form of HAM/TSP while the estimated incidence of adult HAM/TSP is 3%. As there are no curative treatments for HTLV-1 infection (or vaccines) or most of its associated diseases, prevention of infection is fundamental, mainly by vertical transmission, as it is responsible for the development of IDH, infantojuvenile HAM/TSP, and ATL. Public measures to reduce this transmission must be implemented urgently. Furthermore, it is recommended, mainly in HTLV-1 endemic areas, to search for HTLV-1 infection in all patients with infected eczema, even in adults.
Topics: Humans; HTLV-I Infections; Human T-lymphotropic virus 1; Brazil; Paraparesis, Tropical Spastic; Adult; Dermatitis
PubMed: 38697604
DOI: 10.1016/j.ijid.2024.107058 -
Virus Research Oct 2023To review the available studies on the frequency of detection of the bovine leukemia virus in human samples, a systematic review with meta-analysis of the scientific... (Meta-Analysis)
Meta-Analysis
To review the available studies on the frequency of detection of the bovine leukemia virus in human samples, a systematic review with meta-analysis of the scientific literature was carried out, including papers published in English, Spanish, and Portuguese in 5 multidisciplinary databases. We collected information from different populations following a detailed and reproducible search protocol in which two researchers verified the inclusion and exclusion criteria. We identified 759 articles, of which only 33 met the inclusion criteria. Analyzed studies reported that the presence of the virus was measured in human samples, such as paraffin-embedded breast tissue and peripheral blood from 10,398 individuals, through serological and molecular techniques. An overall virus frequency of 27% (Ranging between 17 and 37%) was observed, with a high-frequency data heterogeneity between studies. The presence of this virus in different human biological samples suggests the need to investigate further its transmission route to humans and its potential role in developing and progressing diseases.
Topics: Humans; Leukemia Virus, Bovine
PubMed: 37532141
DOI: 10.1016/j.virusres.2023.199186 -
The Lancet. Microbe Apr 2024Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus associated with substantial risk of secondary (often life-threatening) disease for the estimated 10 million to... (Review)
Review
Human T-lymphotropic virus type 1 and antiretroviral therapy: practical considerations for pre-exposure and post-exposure prophylaxis, transmission prevention, and mitigation of severe disease.
Human T-lymphotropic virus type 1 (HTLV-1) is a retrovirus associated with substantial risk of secondary (often life-threatening) disease for the estimated 10 million to 20 million people infected globally. Despite a clear need, no HTLV-1-specific vaccine or antiretroviral therapy has been developed to date. Instead, existing public and primary health-care interventions inadequately focus on infection prevention and management of secondary diseases. In this Personal View, we discuss the evidence that exists to support the sensitivity of HTLV-1 to antiretroviral therapies approved by the US Food and Drug Administration for the treatment of HIV-1, how this sensitivity is affected by clinically relevant virological and immunological features, and additional practical considerations for the use of antiretroviral therapies in the context of HTLV-1.
Topics: United States; Humans; Human T-lymphotropic virus 1; Post-Exposure Prophylaxis; HIV Infections; HIV-1
PubMed: 38246188
DOI: 10.1016/S2666-5247(23)00359-2 -
Virology Journal Dec 2023Human T-lymphotropic virus 1 (HTLV-1) is associated with the development of several pathologies and chronic infection in humans. The inefficiency of the available...
BACKGROUND
Human T-lymphotropic virus 1 (HTLV-1) is associated with the development of several pathologies and chronic infection in humans. The inefficiency of the available treatments and the challenge in developing a protective vaccine highlight the need to produce effective immunotherapeutic tools. The HTLV-1 basic leucine zipper (bZIP) factor (HBZ) plays an important role in the HTLV-1 persistence, conferring a survival advantage to infected cells by reducing the HTLV-1 proteins expression, allowing infected cells to evade immune surveillance, and enhancing cell proliferation leading to increased proviral load.
METHODS
We have generated a recombinant Modified Virus Vaccinia Ankara (MVA-HBZ) and a plasmid DNA (pcDNA3.1(+)-HBZ) expressing a multiepitope protein based on peptides of HBZ to study the immunogenic potential of this viral-derived protein in BALB/c mice model. Mice were immunized in a prime-boost heterologous protocol and their splenocytes (T CD4 and T CD8) were immunophenotyped by flow cytometry and the humoral response was evaluated by ELISA using HBZ protein produced in prokaryotic vector as antigen.
RESULTS
T CD4 and T CD8 lymphocytes cells stimulated by HBZ-peptides (HBZ and HBZ) showed polyfunctional double positive responses for TNF-α/IFN-γ, and TNF-α/IL-2. Moreover, T CD8 cells presented a tendency in the activation of effector memory cells producing granzyme B (CD44/CD62L), and the activation of Cytotoxic T Lymphocytes (CTLs) and cytotoxic responses in immunized mice were inferred through the production of granzyme B by effector memory T cells and the expression of CD107a by CD8 T cells. The overall data is consistent with a directive and effector recall response, which may be able to operate actively in the elimination of HTLV-1-infected cells and, consequently, in the reduction of the proviral load. Sera from immunized mice, differently from those of control animals, showed IgG-anti-HBZ production by ELISA.
CONCLUSIONS
Our results highlight the potential of the HBZ multiepitope protein expressed from plasmid DNA and a poxviral vector as candidates for therapeutic vaccine.
Topics: Mice; Humans; Animals; Human T-lymphotropic virus 1; CD8-Positive T-Lymphocytes; Granzymes; Tumor Necrosis Factor-alpha; Vaccines, DNA; Viral Proteins; Vaccinia virus; DNA; Basic-Leucine Zipper Transcription Factors; Retroviridae Proteins
PubMed: 38115107
DOI: 10.1186/s12985-023-02264-z -
Nucleic Acids Research Feb 2024The NF-κB protein p65/RelA plays a pivotal role in coordinating gene expression in response to diverse stimuli, including viral infections. At the chromatin level,...
The NF-κB protein p65/RelA plays a pivotal role in coordinating gene expression in response to diverse stimuli, including viral infections. At the chromatin level, p65/RelA regulates gene transcription and alternative splicing through promoter enrichment and genomic exon occupancy, respectively. The intricate ways in which p65/RelA simultaneously governs these functions across various genes remain to be fully elucidated. In this study, we employed the HTLV-1 Tax oncoprotein, a potent activator of NF-κB, to investigate its influence on the three-dimensional organization of the genome, a key factor in gene regulation. We discovered that Tax restructures the 3D genomic landscape, bringing together genes based on their regulation and splicing patterns. Notably, we found that the Tax-induced gene-gene contact between the two master genes NFKBIA and RELA is associated with their respective changes in gene expression and alternative splicing. Through dCas9-mediated approaches, we demonstrated that NFKBIA-RELA interaction is required for alternative splicing regulation and is caused by an intragenic enrichment of p65/RelA on RELA. Our findings shed light on new regulatory mechanisms upon HTLV-1 Tax and underscore the integral role of p65/RelA in coordinated regulation of NF-κB-responsive genes at both transcriptional and splicing levels in the context of the 3D genome.
Topics: Alternative Splicing; Chromatin Assembly and Disassembly; Gene Products, tax; Human T-lymphotropic virus 1; NF-kappa B; Signal Transduction; Transcription Factor RelA; Transcriptional Activation; Humans; NF-kappa B p50 Subunit; Gene Expression Regulation
PubMed: 38272542
DOI: 10.1093/nar/gkae015 -
Molecular Therapy : the Journal of the... Jul 2023The human T cell leukemia virus type 1 (HTLV-1) is a pathogenic retrovirus that persists as a provirus in the genome of infected cells and can lead to adult T cell...
The human T cell leukemia virus type 1 (HTLV-1) is a pathogenic retrovirus that persists as a provirus in the genome of infected cells and can lead to adult T cell leukemia (ATL). Worldwide, more than 10 million people are infected and approximately 5% of these individuals will develop ATL, a highly aggressive cancer that is currently incurable. In the last years, genome editing tools have emerged as promising antiviral agents. In this proof-of-concept study, we use substrate-linked directed evolution (SLiDE) to engineer Cre-derived site-specific recombinases to excise the HTLV-1 proviral genome from infected cells. We identified a conserved loxP-like sequence (loxHTLV) present in the long terminal repeats of the majority of virus isolates. After 181 cycles of SLiDE, we isolated a designer-recombinase (designated RecHTLV), which efficiently recombines the loxHTLV sequence in bacteria and human cells with high specificity. Expression of RecHTLV in human Jurkat T cells resulted in antiviral activity when challenged with an HTLV-1 infection. Moreover, expression of RecHTLV in chronically infected SP cells led to the excision of HTLV-1 proviral DNA. Our data suggest that recombinase-mediated excision of the HTLV-1 provirus represents a promising approach to reduce proviral load in HTLV-1-infected individuals, potentially preventing the development of HTLV-1-associated diseases.
Topics: Adult; Humans; Human T-lymphotropic virus 1; Paraparesis, Tropical Spastic; Proviruses; Antiviral Agents
PubMed: 36934299
DOI: 10.1016/j.ymthe.2023.03.014 -
Veterinarni Medicina Oct 2023Enzootic bovine leucosis is caused by bovine leukaemia virus (BLV), a belonging to the family . BLV causes huge economic losses to the dairy industry in the form...
Enzootic bovine leucosis is caused by bovine leukaemia virus (BLV), a belonging to the family . BLV causes huge economic losses to the dairy industry in the form of decreased milk production, premature culling, and poor reproductive performance of the animals. The aim of the present study was to determine the seroprevalence of BLV infection in buffalo in two districts of Punjab, Pakistan. A total of 384 samples were collected and analysed using a commercial indirect enzyme-linked immunosorbent assay (ELISA) to investigate the seroprevalence of BLV through the detection of the anti-BLV gp51 antibody. A predesigned data questionnaire proforma was employed to find out the association of risk factors with disease. Overall, 18.2% of buffaloes were seropositive for BLV in the study population. The results revealed a significant association ( < 0.05) of age with BLV infection. Furthermore, milk yield and pregnancy had a significant association with the seroprevalence of BLV infection in buffalo whereas no significant association was found with sex, breeding, and health status. Biochemical and oxidative stress markers revealed a significant decrease in liver enzymes alanine transaminase (ALT) and aspartate transaminase (AST), glutathione peroxidase (GPX), and superoxide dismutase (SOD) in seropositive animals as compared to healthy animals. It is concluded that BLV has a considerable prevalence in buffalo in Punjab, Pakistan and there is a dire need to investigate the disease epidemiology at both national and international levels and strategies should be developed to implement an effective control program.
PubMed: 38028205
DOI: 10.17221/57/2023-VETMED -
BioRxiv : the Preprint Server For... Jul 2023Human T-cell leukemia virus type 1 (HTLV-1) has an atypical immature particle morphology compared to other retroviruses. This indicates that these particles are formed...
Human T-cell leukemia virus type 1 (HTLV-1) has an atypical immature particle morphology compared to other retroviruses. This indicates that these particles are formed in a way that is unique. Here we report the results of cryo-electron tomography (cryo-ET) studies of HTLV-1 virus-like particles (VLPs) assembled , as well as derived from cells. This work shows that HTLV-1 employs an unconventional mechanism of Gag-Gag interactions to form the immature viral lattice. Analysis of high-resolution structural information from immature CA tubular arrays reveals that the primary stabilizing component in HTLV-1 is CA-NTD. Mutagenesis and biophysical analysis support this observation. This distinguishes HTLV-1 from other retroviruses, in which the stabilization is provided primarily by the CA-CTD. These results are the first to provide structural details of the quaternary arrangement of Gag for an immature deltaretrovirus, and this helps explain why HTLV-1 particles are morphologically distinct.
PubMed: 37546793
DOI: 10.1101/2023.07.24.548988 -
Tropical Animal Health and Production Sep 2023Enzootic bovine leukosis (EBL) is a chronic infectious disease caused by the bovine leukosis virus (BLV), a Deltaretrovirus. Bovine viral diarrhea (BVD) is an infectious...
Enzootic bovine leukosis (EBL) is a chronic infectious disease caused by the bovine leukosis virus (BLV), a Deltaretrovirus. Bovine viral diarrhea (BVD) is an infectious disease caused by a pestivirus. Bovine neosporosis is caused by the obligate intracellular parasite Neospora caninum (Nc). These pathogens can have horizontal (postnatal) or vertical (transplacental) transmissions and affect the productive and reproductive performance of infected bovines. This work aimed to detect BLV, BVD, and Nc seroprevalence in specialized dairy cattle from the north, east, and Aburrá Valley regions of the Department of Antioquia, the highest in milk production regions in Antioquia. A total of 599 blood samples, obtained from 53 specialized dairy cattle herds, were evaluated by the ELISA test. The results revealed a seroprevalence of 41.13% for BLV (242/599), 28.48% (163/599) for Nc, and 22.7% (132/599) for BVD. Regarding the regional seroprevalence evaluation, BLV was found in 47.02% of the samples from the east, 36.87% from the north, and 46.02% from the Aburrá Valley. Nc was found in 31.03% of the samples from the east, 24.26% from the north, and 36.63% from Aburrá Valley. BVD was found in 21.62% of the samples from the east, 25.03% from the north region, and 10.39% of the samples from the Aburrá Valley. It is highlighted by these results that the north region, with the highest milk production in Antioquia, had the lowest BLV and Nc seroprevalences but the highest seroprevalence of BVD. BLV has increased in Antioquia in recent years, and as an immunosuppressive infection, opportunities for other pathogens are created by it. A significant statistical difference was found in the average prevalence of the pathogens according to the municipality, cattle breed, and region of origin of the sample. The seroprevalence of these pathogens in specialized dairy herds in Antioquia can be classified as medium-low. However, it is recommended that biosecurity practices should be maximized to avoid the spread of these pathogens due to the variability detected in the region, municipality, breed group, and herd age. The rapid and efficient diagnosis of these three pathogens through reliable methodologies will allow for the control of dissemination in dairy herds.
Topics: Animals; Cattle; Colombia; Enzootic Bovine Leukosis; Leukemia Virus, Bovine; Seroepidemiologic Studies; Neospora; Communicable Diseases; Diarrhea; Cattle Diseases
PubMed: 37656253
DOI: 10.1007/s11250-023-03685-2