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PLoS Pathogens Mar 2024A typical HTLV-1-infected individual carries >104 different HTLV-1-infected T cell clones, each with a single-copy provirus integrated in a unique genomic site. We...
A typical HTLV-1-infected individual carries >104 different HTLV-1-infected T cell clones, each with a single-copy provirus integrated in a unique genomic site. We previously showed that the HTLV-1 provirus causes aberrant transcription in the flanking host genome and, by binding the chromatin architectural protein CTCF, forms abnormal chromatin loops with the host genome. However, it remained unknown whether these effects were exerted simply by the presence of the provirus or were induced by its transcription. To answer this question, we sorted HTLV-1-infected T-cell clones into cells positive or negative for proviral plus-strand expression, and then quantified host and provirus transcription using RNA-seq, and chromatin looping using quantitative chromosome conformation capture (q4C), in each cell population. We found that proviral plus-strand transcription induces aberrant transcription and splicing in the flanking genome but suppresses aberrant chromatin loop formation with the nearby host chromatin. Reducing provirus-induced host transcription with an inhibitor of transcriptional elongation allows recovery of chromatin loops in the plus-strand-expressing population. We conclude that aberrant host transcription induced by proviral expression causes temporary, reversible disruption of chromatin looping in the vicinity of the provirus.
Topics: Human T-lymphotropic virus 1; Chromatin; Proviruses; T-Lymphocytes
PubMed: 38427693
DOI: 10.1371/journal.ppat.1011716 -
Retrovirology Feb 2024Human immunodeficiency virus (HIV) and human T cell leukemia virus (HTLV) have replicative and latent stages of infection. The status of the viruses is dependent on the... (Review)
Review
Human immunodeficiency virus (HIV) and human T cell leukemia virus (HTLV) have replicative and latent stages of infection. The status of the viruses is dependent on the cells that harbour them and on different events that change the transcriptional and post-transcriptional events. Non-coding (nc)RNAs are key factors in the regulation of retrovirus replication cycles. Notably, micro (mi)RNAs and long non-coding (lnc)RNAs are important regulators that can induce switches between active transcription-replication and latency of retroviruses and have important impacts on their pathogenesis. Here, we review the functions of miRNAs and lncRNAs in the context of HIV and HTLV. We describe how specific miRNAs and lncRNAs are involved in the regulation of the viruses' transcription, post-transcriptional regulation and latency. We further discuss treatment strategies using ncRNAs for HIV and HTLV long remission, reactivation or possible cure.
Topics: Humans; MicroRNAs; RNA, Long Noncoding; HIV; Gene Expression Regulation; RNA, Untranslated; Deltaretrovirus; Retroviridae; HIV Infections
PubMed: 38424561
DOI: 10.1186/s12977-024-00637-y -
Viruses Feb 2024To mediate intercellular communication, cells produce extracellular vesicles (EVs). These EVs transport many biomolecules such as proteins, nucleic acids, and lipids...
To mediate intercellular communication, cells produce extracellular vesicles (EVs). These EVs transport many biomolecules such as proteins, nucleic acids, and lipids between cells and regulate pathophysiological actions in the recipient cell. However, EVs and virus particles produced from virus-infected cells are of similar size and specific gravity; therefore, the separation and purification of these two particles is often controversial. When analyzing the physiological functions of EVs from virus-infected cells, the presence or absence of virus particle contamination must always be verified. The human T-cell leukemia virus type 1 (HTLV-1)-infected cell line, MT-2, produces EVs and virus particles. Here, we validated a method for purifying EVs from MT-2 cell culture supernatants while avoiding HTLV-1 viral particle contamination. EV fractions were collected using a combination of immunoprecipitation with Tim-4, which binds to phosphatidylserine, and polymer precipitation. The HTLV-1 viral envelope protein, gp46, was not detected in the EV fraction. Proteomic analysis revealed that EV-constituted proteins were predominant in this EV fraction. Furthermore, the EVs were found to contain the HTLV-1 viral genome. The proposed method can purify EVs while avoiding virus particle contamination and is expected to contribute to future research on EVs derived from HTLV-1-infected cells.
Topics: Humans; Human T-lymphotropic virus 1; Proteomics; Proteins; Leukemia, T-Cell; Virion; Extracellular Vesicles
PubMed: 38400025
DOI: 10.3390/v16020249 -
Pathogens (Basel, Switzerland) Feb 2024We have characterized the intrahost genetic variation in the bovine leukemia virus (BLV) by examining 16 BLV isolates originating from the Western Siberia-Tyumen and...
We have characterized the intrahost genetic variation in the bovine leukemia virus (BLV) by examining 16 BLV isolates originating from the Western Siberia-Tyumen and South Ural-Chelyabinsk regions of Russia. Our research focused on determining the genetic composition of an 804 bp fragment of the BLV gene, encoding for the entire gp51 protein. The results provide the first indication of the quasi-species genetic nature of BLV infection and its relevance for genome-level variation. Furthermore, this is the first phylogenetic evidence for the existence of a dual infection with BLV strains belonging to different genotypes within the same host: G4 and G7. We identified eight cases of recombination between these two BLV genotypes. The detection of quasi-species with cases of dual infection and recombination indicated a higher potential of BLV for genetic variability at the intra-host level than was previously considered.
PubMed: 38392916
DOI: 10.3390/pathogens13020178 -
Archives of Virology Feb 2024Bovine leukemia virus (BLV) is a member of the family Retroviridae that causes enzootic bovine leukemia (EBL). However, the association between BLV infection and EBL...
Bovine leukemia virus (BLV) is a member of the family Retroviridae that causes enzootic bovine leukemia (EBL). However, the association between BLV infection and EBL development remains unclear. In this study, we identified a BLV/SMAD3 chimeric provirus within CC2D2A intron 30 in monoclonal expanded malignant cells from a cow with EBL. The chimeric provirus harbored a spliced SMAD3 sequence composed of exons 3-9, encoding the short isoform protein, and the BLV-SMAD3 chimeric transcript was detectable in cattle with EBL. This is the first report of a BLV chimeric provirus that might be involved in EBL tumorigenesis.
Topics: Animals; Female; Cattle; Enzootic Bovine Leukosis; Proviruses; Leukemia Virus, Bovine
PubMed: 38366081
DOI: 10.1007/s00705-024-05970-3 -
Virus Genes Apr 2024Bovine leukemia virus is a retrovirus that causes enzootic bovine leukosis and is associated with global economic losses in the livestock industry. The aim of this study...
Bovine leukemia virus is a retrovirus that causes enzootic bovine leukosis and is associated with global economic losses in the livestock industry. The aim of this study was to investigate the genotype determination of BLVs from cattle housed in 6 different farms in Türkiye and the characterization of their LTR and pX (tax, rex, R3, and G4 gene) regions. For this purpose, blood samples from 48 cattle infected with BLV were used. The phylogenetic analysis based on the env gene sequences revealed that all BLVs were clustered in genotype 1 (G1), and the sequences of the LTR (n = 48) and the pX region (n = 33) of BLVs were obtained. Also, analysis of these nucleic acid and amino acid sequences allowed assessments similar to those reported in earlier studies to be relevant to transactivation and pathogenesis. This study reports the molecular analysis of the LTR and pX region of BLVs in Türkiye for the first time.
Topics: Animals; Cattle; Genes, env; Leukemia Virus, Bovine; Phylogeny; Turkey; Amino Acid Sequence
PubMed: 38355991
DOI: 10.1007/s11262-024-02058-7 -
Pathology, Research and Practice Mar 2024Adult T-cell leukemia/lymphoma (ATLL) is a rare and aggressive form of cancer associated with human T-cell lymphotropic virus type 1 (HTLV-1) infection. The emerging... (Review)
Review
Adult T-cell leukemia/lymphoma (ATLL) is a rare and aggressive form of cancer associated with human T-cell lymphotropic virus type 1 (HTLV-1) infection. The emerging field of stem cell therapies for ATLL is discussed, highlighting the potential of hematopoietic stem cell transplantation (HSCT) and genetically modified stem cells. HSCT aims to eradicate malignant T-cells and restore a functional immune system through the infusion of healthy donor stem cells. Genetically modified stem cells show promise in enhancing their ability to target and eliminate ATLL cells. The article presents insights from preclinical studies and limited clinical trials, emphasizing the need for further research to establish the safety, efficacy, and long-term outcomes of stem cell therapies for ATLL and challenges associated with these innovative approaches are also explored. Overall, stem cell therapies hold significant potential in revolutionizing ATLL treatment, and ongoing clinical trials aim to determine their benefits in larger patient populations.
Topics: Adult; Humans; Leukemia-Lymphoma, Adult T-Cell; Human T-lymphotropic virus 1; Hematopoietic Stem Cell Transplantation; Lymphoma
PubMed: 38340584
DOI: 10.1016/j.prp.2024.155172 -
American Journal of Veterinary Research Apr 2024The objective of this study was to determine the seroprevalence of reproductive and infectious diseases in tropical cattle in the Tambopata and Tahuamanu Provinces in...
OBJECTIVE
The objective of this study was to determine the seroprevalence of reproductive and infectious diseases in tropical cattle in the Tambopata and Tahuamanu Provinces in the department of Madre de Dios, Peru.
SAMPLE
156 bovines from 7 cattle farms were sampled. These farms used exclusive grazing for food and natural mating for reproduction and did not have sanitary or vaccination programs.
METHODS
The serum of blood samples was subjected to ELISA with commercial kits for the detection of antibodies against Neospora caninum, Mycobacterium avium subsp paratuberculosis (MAP), Leptospira interrogans, pestivirus bovine viral diarrhea virus-1, retrovirus bovine leukemia virus (BLV), orbivirus bluetongue virus (BTV), and herpesvirus bovine herpes virus-1 (BHV). The data were analyzed by means of association tests with χ2 (P < .05) and Spearman rank correlation (P < .05) in the SPSS v.15.0 software (IBM Corp).
RESULTS
A low prevalence of antibodies to L interrogans, N caninum, M avium subsp paratuberculosis, bovine viral diarrhea virus-1 was found, but it was high to BTV, BLV, and BHV (100%, 53.85%, and 72.44%, respectively). The presence of BLV and BHV was higher in the Las Piedras District, bovines less than 5 years old, and cattle with breed characteristics of zebu and crossbred (P < .01). In addition, there was a significant correlation between both infections, showing 83.3% of BLV positivity that were also BHV positive (P < .01).
CLINICAL RELEVANCE
The high prevalence of antibodies to BTV, BHV, and BLV could be due to livestock management practices, direct contact with infected animals, and variation of the presence of vectors and natural reservoirs in the context of climate change in the tropics.
Topics: Cattle; Animals; Paratuberculosis; Cattle Diseases; Enzootic Bovine Leukosis; Bovine Virus Diarrhea-Mucosal Disease; Peru; Seroepidemiologic Studies; Diarrhea Viruses, Bovine Viral; Antibodies, Viral; Antibodies, Bacterial; Communicable Diseases; Reproduction; Diarrhea Virus 1, Bovine Viral; Leukemia Virus, Bovine; Diarrhea
PubMed: 38335721
DOI: 10.2460/ajvr.23.08.0177 -
Frontiers in Public Health 2024Human T Lymphotropic Virus type 1 (HTLV-1) is a neglected retrovirus associated with many clinical disorders, most notably Adult T-cell Leukemia/Lymphoma and... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Human T Lymphotropic Virus type 1 (HTLV-1) is a neglected retrovirus associated with many clinical disorders, most notably Adult T-cell Leukemia/Lymphoma and HTLV-1-Associated Myelopathy (HAM). Found in endemic clusters across the world, high prevalence has been reported in minoritized groups who suffer from health inequities. This study investigates the association between HTLV-1 prevalence and the following socioeconomic determinants of health: education, income, and employment, which are markers of health inequity.
METHODS
A systematic review was conducted by searching the following databases: Ovid/Medline, Embase, Global Health Database, Web of Science, LILACS and SciELO. Primary studies in English, Spanish and Portuguese mentioning HTLV-1 and one of education, income and/or employment were included. A random-effects meta-analysis was performed, and odds ratios (OR) were calculated to determine the association between these socioeconomic determinants of health and HTLV-1 prevalence.
RESULTS
42 studies were included. The likelihood of having HTLV-1 was higher in individuals with less than completed primary education compared to those who completed primary education (OR 1.86 [95% CI 1.34-2.57]; < 0.01). This may be because individuals with low education have reduced access to and understanding of health information, thus increasing the prevalence of risk factors associated with HTLV-1 infection. No other determinants were found to be statistically significant.
CONCLUSION
Fewer years of schooling are associated with increased likelihood of contracting HTLV-1. Therefore, health promotion materials and public health policies regarding HTLV-1 must consider those with lower educational levels to effectively reduce disease transmission.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=335004, identifier (CRD42022335004).
Topics: Humans; Adult; Human T-lymphotropic virus 1; HTLV-I Infections; Paraparesis, Tropical Spastic; Risk Factors; Socioeconomic Factors
PubMed: 38327581
DOI: 10.3389/fpubh.2024.1298308 -
Human Genomics Feb 2024Periodic bioinformatics-based screening of wastewater for assessing the diversity of potential human viral pathogens circulating in a given community may help to...
BACKGROUND
Periodic bioinformatics-based screening of wastewater for assessing the diversity of potential human viral pathogens circulating in a given community may help to identify novel or potentially emerging infectious diseases. Any identified contigs related to novel or emerging viruses should be confirmed with targeted wastewater and clinical testing.
RESULTS
During the COVID-19 pandemic, untreated wastewater samples were collected for a 1-year period from the Great Lakes Water Authority Wastewater Treatment Facility in Detroit, MI, USA, and viral population diversity from both centralized interceptor sites and localized neighborhood sewersheds was investigated. Clinical cases of the diseases caused by human viruses were tabulated and compared with data from viral wastewater monitoring. In addition to Betacoronavirus, comparison using assembled contigs against a custom Swiss-Prot human virus database indicated the potential prevalence of other pathogenic virus genera, including: Orthopoxvirus, Rhadinovirus, Parapoxvirus, Varicellovirus, Hepatovirus, Simplexvirus, Bocaparvovirus, Molluscipoxvirus, Parechovirus, Roseolovirus, Lymphocryptovirus, Alphavirus, Spumavirus, Lentivirus, Deltaretrovirus, Enterovirus, Kobuvirus, Gammaretrovirus, Cardiovirus, Erythroparvovirus, Salivirus, Rubivirus, Orthohepevirus, Cytomegalovirus, Norovirus, and Mamastrovirus. Four nearly complete genomes were recovered from the Astrovirus, Enterovirus, Norovirus and Betapolyomavirus genera and viral species were identified.
CONCLUSIONS
The presented findings in wastewater samples are primarily at the genus level and can serve as a preliminary "screening" tool that may serve as indication to initiate further testing for the confirmation of the presence of species that may be associated with human disease. Integrating innovative environmental microbiology technologies like metagenomic sequencing with viral epidemiology offers a significant opportunity to improve the monitoring of, and predictive intelligence for, pathogenic viruses, using wastewater.
Topics: Humans; Wastewater; Michigan; Pandemics; Viruses; Enterovirus; Virus Diseases
PubMed: 38321488
DOI: 10.1186/s40246-024-00581-0