-
Microbiology Spectrum Dec 2023The World Health Organization estimated that 5-10 million people are infected with human T-cell leukemia virus type 1 (HTLV-1). This number is likely to be...
The World Health Organization estimated that 5-10 million people are infected with human T-cell leukemia virus type 1 (HTLV-1). This number is likely to be underestimated because reliable endemic data are available for only approximately 1.5 billion people worldwide. The point-of-care test is a powerful tool for the easy and quick detection of infections without the requirement for expensive instruments and laboratory equipment. Espline HTLV-I/II, a newly developed rapid immunochromatographic antibody test that was evaluated in this study, might significantly advance our understanding of the global epidemiology of HTLV-1 infection.
Topics: Humans; Human T-lymphotropic virus 1; HTLV-I Infections
PubMed: 37966220
DOI: 10.1128/spectrum.02078-23 -
Chemical & Pharmaceutical Bulletin 2024The inhibition mode of a retro-inverso (RI) inhibitor containing a hydroxyethylamine dipeptide isostere against the human T-cell leukemia virus type-1 (HTLV-1) protease...
The inhibition mode of a retro-inverso (RI) inhibitor containing a hydroxyethylamine dipeptide isostere against the human T-cell leukemia virus type-1 (HTLV-1) protease was examined. Enzymatic evaluation of the RI-modified inhibitor containing a D-allo-Ile residue revealed that HTLV-1 was competitively inhibited. IC values of the RI-modified inhibitor and pepstatin A, a standard inhibitor of aspartic proteases, were nearly equivalent.
Topics: Humans; Amino Acid Sequence; Aspartic Acid Endopeptidases; Human T-lymphotropic virus 1; Dipeptides; Protease Inhibitors
PubMed: 38479891
DOI: 10.1248/cpb.c23-00879 -
Scientific Reports Dec 2023Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leucosis (EBL), which has been reported worldwide. The expression of viral structural proteins:...
Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leucosis (EBL), which has been reported worldwide. The expression of viral structural proteins: surface glycoprotein (gp51) and three core proteins - p15 (matrix), p24 (capsid), and p12 (nucleocapsid) induce a strong humoral and cellular immune response at first step of infection. CD4+ T-cell activation is generally induced by bovine leukocyte antigen (BoLA) region- positive antigen-presenting cells (APC) after processing of an exogenous viral antigen. Limited data are available on the BLV epitopes from the core proteins recognized by CD4+ T-cells. Thus, immunoinformatic analysis of Gag sequences obtained from 125 BLV isolates from Poland, Canada, Pakistan, Kazakhstan, Moldova and United States was performed to identify the presence of BoLA-DRB3 restricted CD4+ T-cell epitopes. The 379 15-mer overlapping peptides spanning the entire Gag sequence were run in BoLA-DRB3 allele-binding regions using a BoLA-DRB- peptide binding affinity prediction algorithm. The analysis identified 22 CD4+ T-cell peptide epitopes of variable length ranging from 17 to 22 amino acids. The predicted epitopes interacted with 73 different BoLA-DRB3 alleles found in BLV-infected cattle. Importantly, two epitopes were found to be linked with high proviral load in PBMC. A majority of dominant and subdominant epitopes showed high conservation across different viral strains, and therefore could be attractive targets for vaccine development.
Topics: Animals; Cattle; CD4-Positive T-Lymphocytes; Epitopes, T-Lymphocyte; Leukemia Virus, Bovine; Gene Products, gag; Leukocytes, Mononuclear; HLA-DR Antigens; Peptides
PubMed: 38102157
DOI: 10.1038/s41598-023-48899-4 -
Frontiers in Public Health 2024Studies on human T-lymphotropic virus 1/2 (HTLV-1/2) infection are scarce in incarcerated population. Therefore, this study estimated the prevalence of HTLV-1/2...
INTRODUCTION
Studies on human T-lymphotropic virus 1/2 (HTLV-1/2) infection are scarce in incarcerated population. Therefore, this study estimated the prevalence of HTLV-1/2 infection among prisoners of the major penitentiary complex of Goiás State, Central-West Brazil, comparing it with available data from other Brazilian regions.
METHODS
A cross-sectional study was conducted with 910 prisoners of the major penitentiary complex in the State of Goiás, Central-West Brazil. All participants were interviewed, and their serum samples were tested for anti-HTLV-1/2 using an enzyme-linked immunosorbent assay (ELISA; Murex HTLV-I + II, DiaSorin, Dartford, UK). Seropositive samples were submitted for confirmation by a line immunoassay (INNO-LIA HTLV I/II, Fujirebio, Europe N.V., Belgium).
RESULTS
The majority of participants were males (83.1%), between 25 and 39 years old (56.1%; mean age: 31.98 years), self-reported brown ethnicity (56.2%) and reported 9 years or less of formal education (41.4%). Most reported using non-injectable illicit drugs and various sexual behaviors that present risk for sexually transmitted infections (STIs). The prevalence of anti-HTLV-1/2 was 0.33% (95% CI: 0.07-0.96), HTLV-1 (0.22%) and HTLV-2 (0.11%). The two HTLV-1 seropositive prisoners reported high-risk sexual behaviors, and the HTLV-2 seropositive individual was breastfed during childhood (> 6 months) by her mother and three other women.
CONCLUSION
These data revealed a relatively low seroprevalence of HTLV-1/2 in prisoners in Central-West Brazil, and evidence of HTLV-1 and HTLV-2 circulation in the major penitentiary complex of Goiás State. Given the prevalence of high-risk sexual behaviors, there is a crucial need to intensify education and health programs in prisons to effectively control and prevent HTLV-1/2 and other STIs.
Topics: Humans; Brazil; Cross-Sectional Studies; HTLV-I Infections; Adult; HTLV-II Infections; Male; Female; Prisoners; Prevalence; Human T-lymphotropic virus 1; Human T-lymphotropic virus 2; Middle Aged; Enzyme-Linked Immunosorbent Assay; Young Adult
PubMed: 38706549
DOI: 10.3389/fpubh.2024.1379237 -
Microbiology Spectrum Aug 2023Human T-cell leukemia virus type 1 (HTLV-1) induces chronic asymptomatic latent infection with a substantial proviral load but without significant viral replication ....
Human T-cell leukemia virus type 1 (HTLV-1) induces chronic asymptomatic latent infection with a substantial proviral load but without significant viral replication . Cumulative studies have indicated involvement of CD8-positive (CD8) cells, including virus-specific CD8 T cells in the control of HTLV-1 replication. However, whether HTLV-1 expression from latently infected cells occurs in the absence of CD8 cells remains unclear. Here, we examined the impact of CD8 cell depletion by monoclonal anti-CD8 antibody administration on proviral load in HTLV-1-infected cynomolgus macaques. Five cynomolgus macaques were infected with HTLV-1 by inoculation with HTLV-1-producing cells. Administration of monoclonal anti-CD8 antibody in the chronic phase resulted in complete depletion of peripheral CD8 T cells for approximately 2 months. All five macaques showed an increase in proviral load following CD8 cell depletion, which peaked just before the reappearance of peripheral CD8 T cells. Tax-specific CD8 T-cell responses were detected in these recovered CD8 T cells. Importantly, anti-HTLV-1 antibodies also increased after CD8 cell depletion, indicating HTLV-1 antigen expression. These results provide evidence indicating that HTLV-1 can proliferate from the latent phase in the absence of CD8 cells and suggest that CD8 cells are responsible for the control of HTLV-1 replication. HTLV-1 can cause serious diseases such as adult T-cell leukemia (ATL) in humans after chronic asymptomatic latent infection with substantial proviral load. Proviruses are detectable in peripheral lymphocytes in HTLV-1 carriers, and the association of a higher proviral load with a higher risk of disease progression has been observed. However, neither substantial viral structural protein expression nor viral replication was detectable . Cumulative studies have indicated involvement of CD8 cells, including virus-specific CD8 T cells in the control of HTLV-1 replication. In the present study, we showed that CD8 cell depletion by monoclonal anti-CD8 antibody administration results in HTLV-1 expression and an increase in proviral load in HTLV-1-infected cynomolgus macaques. Our results indicate that HTLV-1 can proliferate in the absence of CD8 cells, suggesting that CD8 cells are responsible for the control of HTLV-1 replication. This study provides insights into the mechanism of virus-host immune interaction in latent HTLV-1 infection.
Topics: Adult; Animals; Humans; CD8-Positive T-Lymphocytes; Human T-lymphotropic virus 1; Proviruses; Macaca fascicularis; Latent Infection; Cell Proliferation; Viral Load
PubMed: 37367230
DOI: 10.1128/spectrum.01518-23 -
Internal Medicine (Tokyo, Japan) Apr 2024Human T-cell lymphotropic virus type-1 (HTLV-1)-associated bronchioloalveolar disorder (HABA) is a pulmonary disorder characterized by lymphocytic infiltration of the... (Review)
Review
Human T-cell lymphotropic virus type-1 (HTLV-1)-associated bronchioloalveolar disorder (HABA) is a pulmonary disorder characterized by lymphocytic infiltration of the peribronchiolar space and interstitium in HTLV-1 carriers and in adult T-cell leukemia/lymphoma (ATLL). We herein report an 85-year-old woman carrying HTLV-1 with HABA who presented with a miliary pattern of micronodules in both lungs on high-resolution computed tomography and a lymphocytic infiltrate with non-necrotizing granulomas on pathology. This rare case of HABA should be differentiated from sarcoidosis, hypersensitivity pneumonitis, or miliary tuberculosis.
Topics: Adult; Female; Humans; Aged, 80 and over; Human T-lymphotropic virus 1; Leukemia-Lymphoma, Adult T-Cell; Granuloma; T-Lymphocytes; HTLV-I Infections; Azo Compounds
PubMed: 37661452
DOI: 10.2169/internalmedicine.2201-23 -
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 -
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 -
Acta Tropica Aug 2024The Bovine Leukemia Virus (BLV) affects mainly cattle, is transmitted by exposure to contaminated biological fluids, and generates lymphomas in 5 % of infected animals....
The Bovine Leukemia Virus (BLV) affects mainly cattle, is transmitted by exposure to contaminated biological fluids, and generates lymphomas in 5 % of infected animals. The zoonotic potential of BLV has been studied, and it is currently unknown if it circulates in human workers on dairy herds in Antioquia. Objective: To determine the frequency of BLV detection, the genotypes of the virus, and the factors associated with its detection in workers for dairy herds in Antioquia, Colombia. Through a cross-sectional study in 51 dairy herds, 164 adults were recruited. A peripheral blood sample was collected from each participant for molecular detection of the BLV env and tax genes, and associated factors were explored through bivariate and multivariate mixed Poisson model analyses. The analysis showed that 82 % (134/164) of the participants were men, with an average age of 40. Using qPCR, the constitutive gene GAPDH was amplified to evaluate the presence of amplification inhibitors in the DNA samples. Using nested PCR, the amplification of the env viral gene was obtained in 13 % (22/164) of the total samples analyzed, while all the samples tested negative for tax. The amplicons of the env gene were sequenced, and the identity compatible with BLV was verified by BLAST analysis (NCBI). Using molecular phylogeny analysis, based on maximum likelihood and haplotype network analysis, it was identified that BLV genotype 1 is present in the evaluated population. 16 % (26/164) of the participants reported having ever had an accident with surgical material during work with cattle; this variable was associated with BLV positivity even after adjusting for other variables (PRa =2.70, 95 % CI= 1.01- 7.21). Considering that other studies have reported the circulation of BLV genotype 1 in cattle from this same region and the present report in humans from dairy herds, the results suggest a possible zoonotic transmission of BLV genotype 1 in Antioquia, reinforcing the need to continue investigating to determine the potential role of this virus as an etiological agent of disease in livestock farmers in the department.
Topics: Leukemia Virus, Bovine; Colombia; Humans; Female; Cross-Sectional Studies; Adult; Animals; Male; Cattle; Middle Aged; Enzootic Bovine Leukosis; Dairying; Genotype; Young Adult; Phylogeny; Zoonoses; Farmers
PubMed: 38782108
DOI: 10.1016/j.actatropica.2024.107253 -
PloS One 2024To identify a biomarker for the early diagnosis of enzootic bovine leukosis (EBL) caused by bovine leukemia virus (BLV), we investigated the expression of a microRNA,...
To identify a biomarker for the early diagnosis of enzootic bovine leukosis (EBL) caused by bovine leukemia virus (BLV), we investigated the expression of a microRNA, bta-miR-375, in cattle serum. Using quantitative reverse-transcriptase PCR analysis, we measured bta-miR-375 levels in 27 samples from cattle with EBL (EBL cattle), 45 samples from animals infected with BLV but showing no clinical signs (NS cattle), and 30 samples from cattle uninfected with BLV (BLV negative cattle). In this study, we also compared the kinetics of bta-miR-375 with those of the conventional biomarkers of proviral load (PVL), lactate dehydrogenase (LDH), and thymidine kinase (TK) from the no-clinical-sign phase until EBL onset in three BLV-infected Japanese black (JB) cattle. Bta-miR-375 expression was higher in NS cattle than in BLV negative cattle (P < 0.05) and greater in EBL cattle than in BLV negative and NS cattle (P < 0.0001 for both comparisons). Receiver operating characteristic curves demonstrated that bta-miR-375 levels distinguished EBL cattle from NS cattle with high sensitivity and specificity. In NS cattle, bta-miR-375 expression was increased as early as at 2 months before EBL onset-earlier than the expression of PVL, TK, or LDH isoenzymes 2 and 3. These results suggest that serum miR-375 is a promising biomarker for the early diagnosis of EBL.
Topics: Animals; Cattle; Enzootic Bovine Leukosis; MicroRNAs; Biomarkers; Leukemia Virus, Bovine; Early Diagnosis; ROC Curve; L-Lactate Dehydrogenase
PubMed: 38723001
DOI: 10.1371/journal.pone.0302868