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Journal of Dairy Science Dec 2023Bovine leukemia virus (BLV) has spread worldwide and causes serious problems in the cattle industry owing to the lack of effective treatments and vaccines. Bovine...
Effectiveness of integrated bovine leukemia virus eradication strategies utilizing cattle carrying resistant and susceptible major histocompatibility complex class II DRB3 alleles.
Bovine leukemia virus (BLV) has spread worldwide and causes serious problems in the cattle industry owing to the lack of effective treatments and vaccines. Bovine leukemia virus is transmitted via horizontal and vertical infection, and cattle with high BLV proviral load (PVL), which is a useful index for estimating disease progression and transmission risk, are considered major infectious sources within herds. The PVL strongly correlates with highly polymorphic bovine lymphocyte antigen (BoLA)-DRB3 alleles. The BoLA-DRB3*015:01 and *012:01 alleles are known susceptibility-associated markers related to high PVL, and cattle with susceptible alleles may be at a high risk of BLV transmission via direct contact with healthy cows. In contrast, the BoLA-DRB3*009:02 and *014:01:01 alleles comprise resistant markers associated with the development of low PVL, and cattle with resistant alleles may be low-risk spreaders for BLV transmission and disrupt the BLV transmission chain. However, whether polymorphisms in BoLA-DRB3 are useful for BLV eradication in farms remains unknown. Here, we conducted a validation trial of the integrated BLV eradication strategy to prevent new infection by resistant cattle and actively eliminate susceptible cattle in addition to conventional BLV eradication strategies to maximally reduce the BLV prevalence and PVL using a total of 342 cattle at 4 stall-barn farms in Japan from 2017 to 2019. First, we placed the resistant milking cattle between the BLV-positive and BLV-negative milking cattle in a stall barn for 3 yr. Interestingly, the resistant cattle proved to be an effective biological barrier to successfully block the new BLV infections in the stall-barn system among all 4 farms. Concomitantly, we actively eliminated cattle with high PVL, especially susceptible cattle. Indeed, 39 of the 60 susceptible cattle (65%), 76 of the 140 neutral cattle (54%), and 20 of the 41 resistant cattle (48.8%) were culled on 4 farms for 3 years. Consequently, BLV prevalence and mean PVL decreased in all 4 farms. In particular, one farm achieved BLV-free status in May 2020. By decreasing the number of BLV-positive animals, the revenue-enhancing effect was estimated to be ¥5,839,262 ($39,292.39) for the 4 farms over 3 yr. Our results suggest that an integrated BLV eradication program utilization of resistant cattle as a biological barrier and the preferential elimination of susceptible cattle are useful for BLV infection control.
Topics: Animals; Cattle; Female; Alleles; Cattle Diseases; Disease Susceptibility; Enzootic Bovine Leukosis; Histocompatibility Antigens Class II; Leukemia Virus, Bovine; Major Histocompatibility Complex
PubMed: 37641252
DOI: 10.3168/jds.2023-23524 -
Virology Journal Aug 2023HTLV-1-associated uveitis (HAU) is an inflammatory reaction of the choroid, retina, optic nerve and vitreous that can lead to vision impairment. The worldwide prevalence...
BACKGROUND
HTLV-1-associated uveitis (HAU) is an inflammatory reaction of the choroid, retina, optic nerve and vitreous that can lead to vision impairment. The worldwide prevalence of HAU varies widely.
OBJECTIVE
To determine the prevalence of HAU in patients from Salvador, Bahia-Brazil, and describe uveitis type and associated symptoms.
METHODS
Cross-sectional analytical study to determine the prevalence of uveitis in HTLV-1-infected patients recruited in Bahia, Brazil, a region considered endemic for HTLV-1. Patients were enrolled at a local reference center for HTLV (infected) and at an outpatient ophthalmology clinic (noninfected group). All patients were examined by the same ophthalmologist following a single protocol. Prevalence ratios (PR) were calculated.
RESULTS
A total of 168 consecutively examined HTLV-1-infected patients and 410 noninfected patients (randomly selected) were included. Females predominated (82.1%) in the HTLV-1-infected group (versus 64.4% in the uninfected group) (p < 0.001). The mean age of infected and uninfected patients was 53.2 and 62.8 years, respectively (p < 0.001). The prevalence of uveitis in HTLV-1 and HTLV-1 patients was 7.14% and 0.73%, respectively (PR = 9.76; 95CI%:2.79-34.15; p < 0.01). Bilateral intermediate uveitis, associated with symptoms including visual disturbances and floaters, was most commonly identified in the HTLV-1-infected patients, whereas unilateral anterior uveitis, in association with symptoms such as blurring and ocular pain, was more common in the uninfected group.
CONCLUSION
The prevalence of uveitis in patients with HTLV-1 was markedly higher than in uninfected subjects. HAU patients were mostly asymptomatic and exhibited bilateral presentation, with uveitis more frequently localized in the intermediate chamber.
Topics: Female; Humans; Middle Aged; Brazil; Cross-Sectional Studies; Human T-lymphotropic virus 1; Prevalence; Uveitis; Male
PubMed: 37605273
DOI: 10.1186/s12985-023-02135-7 -
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 -
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 -
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 -
PLoS Pathogens Jul 2023Infections by Human T cell Leukaemia Virus type 1 (HTLV-1) persist for the lifetime of the host by integrating into the genome of CD4+ T cells. Proviral gene expression...
Infections by Human T cell Leukaemia Virus type 1 (HTLV-1) persist for the lifetime of the host by integrating into the genome of CD4+ T cells. Proviral gene expression is essential for proviral survival and the maintenance of the proviral load, through the pro-proliferative changes it induces in infected cells. Despite their role in HTLV-1 infection and a persistent cytotoxic T lymphocyte response raised against the virus, proviral transcripts from the sense-strand are rarely detected in fresh cells extracted from the peripheral blood, and have recently been found to be expressed intermittently by a small subset of cells at a given time. Ex vivo culture of infected cells prompts synchronised proviral expression in infected cells from peripheral blood, allowing the study of factors involved in reactivation in primary cells. Here, we used bulk RNA-seq to examine the host transcriptome over six days in vitro, following proviral reactivation in primary peripheral CD4+ T cells isolated from subjects with non-malignant HTLV-1 infection. Infected cells displayed a conserved response to reactivation, characterised by discrete stages of gene expression, cell division and subsequently horizontal transmission of the virus. We observed widespread changes in Polycomb gene expression following reactivation, including an increase in PRC2 transcript levels and diverse changes in the expression of PRC1 components. We hypothesize that these transcriptional changes constitute a negative feedback loop that maintains proviral latency by re-deposition of H2AK119ub1 following the end of proviral expression. Using RNAi, we found that certain deubiquitinases, BAP1, USP14 and OTUD5 each promote proviral transcription. These data demonstrate the detailed trajectory of HTLV-1 proviral reactivation in primary HTLV-1-carrier lymphocytes and the impact on the host cell.
Topics: Humans; Human T-lymphotropic virus 1; Proviruses; HTLV-I Infections; Transcriptome; CD4-Positive T-Lymphocytes; Viral Load; Ubiquitin Thiolesterase
PubMed: 37523412
DOI: 10.1371/journal.ppat.1011494 -
International Journal of Molecular... Jul 2023Adult T cell leukemia (ATL) is an aggressive hematologic disease caused by human T cell leukemia virus type 1 (HTLV-1) infection. Various animal models of HTLV-1... (Review)
Review
Adult T cell leukemia (ATL) is an aggressive hematologic disease caused by human T cell leukemia virus type 1 (HTLV-1) infection. Various animal models of HTLV-1 infection/ATL have been established to elucidate the pathogenesis of ATL and develop appropriate treatments. For analyses employing murine models, transgenic and immunodeficient mice are used because of the low infectivity of HTLV-1 in mice. Each mouse model has different characteristics that must be considered before use for different HTLV-1 research purposes. HTLV-1 and transgenic mice spontaneously develop tumors, and the roles of both Tax and HBZ in cell transformation and tumor growth have been established. Severely immunodeficient mice were able to be engrafted with ATL cell lines and have been used in preclinical studies of candidate molecules for the treatment of ATL. HTLV-1-infected humanized mice with an established human immune system are a suitable model to characterize cells in the early stages of HTLV-1 infection. This review outlines the characteristics of mouse models of HTLV-1 infection/ATL and describes progress made in elucidating the pathogenesis of ATL and developing related therapies using these mice.
Topics: Adult; Mice; Humans; Animals; Leukemia-Lymphoma, Adult T-Cell; Human T-lymphotropic virus 1; Retroviridae Proteins; HTLV-I Infections; Mice, Transgenic; Disease Models, Animal; Basic-Leucine Zipper Transcription Factors
PubMed: 37511495
DOI: 10.3390/ijms241411737 -
Proceedings of the National Academy of... Aug 2023Retroviruses and their host have coevolved in a delicate balance between viral replication and survival of the infected cell. In this equilibrium, restriction factors...
Retroviruses and their host have coevolved in a delicate balance between viral replication and survival of the infected cell. In this equilibrium, restriction factors expressed by infected cells control different steps of retroviral replication such as entry, uncoating, nuclear import, expression, or budding. Here, we describe a mechanism of restriction against human T cell leukemia virus type 1 (HTLV-1) by the helicase-like transcription factor (HLTF). We show that RNA and protein levels of HLTF are reduced in primary T cells of HTLV-1-infected subjects, suggesting a clinical relevance. We further demonstrate that the viral oncogene Tax represses HLTF transcription via the Enhancer of zeste homolog 2 methyltransferase of the Polycomb repressive complex 2. The Tax protein also directly interacts with HLTF and induces its proteasomal degradation. RNA interference and gene transduction in HTLV-1-infected T cells derived from patients indicate that HLTF is a restriction factor. Restoring the normal levels of HLTF expression induces the dispersal of the Golgi apparatus and overproduction of secretory granules. By synergizing with Tax-mediated NF-κB activation, physiologically relevant levels of HLTF intensify the autophagic flux. Increased vesicular trafficking leads to an enlargement of the lysosomes and the production of large vacuoles containing viral particles. HLTF induction in HTLV-1-infected cells significantly increases the percentage of defective virions. In conclusion, HLTF-mediated activation of the autophagic flux blunts the infectious replication cycle of HTLV-1, revealing an original mode of viral restriction.
Topics: Humans; Human T-lymphotropic virus 1; Transcription Factors; Gene Products, tax; T-Lymphocytes; Leukemia, T-Cell; NF-kappa B; DNA-Binding Proteins
PubMed: 37487091
DOI: 10.1073/pnas.2216127120 -
The Lancet. Global Health Aug 2023
Topics: Female; Humans; Pregnancy; Human T-lymphotropic virus 1; Infectious Disease Transmission, Vertical; Breast Feeding; Pregnancy Complications, Infectious
PubMed: 37474224
DOI: 10.1016/S2214-109X(23)00268-1 -
The Lancet. Global Health Aug 2023
Topics: Female; Humans; Pregnancy; Human T-lymphotropic virus 1; Infectious Disease Transmission, Vertical; Breast Feeding; Pregnancy Complications, Infectious
PubMed: 37474223
DOI: 10.1016/S2214-109X(23)00264-4