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International Journal of Infectious... Jun 2024Human T-lymphotropic viruses (HTLV)-1 infection is endemic in many countries of Central and South America and Caribbean (CSA&C). Neither screening nor surveillance... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Human T-lymphotropic viruses (HTLV)-1 infection is endemic in many countries of Central and South America and Caribbean (CSA&C). Neither screening nor surveillance programs exist for HTLV-1/2 infection among pregnant women in this region. Neither in Western nations with large migrant flows from HTLV-1/2 endemic regions.
METHODS
Systematic review and meta-analysis of the prevalence of HTLV-1/2 infection among CSA&C pregnant women. We included studies searching EMBASE, PubMed/MEDLINE, Scopus, and Web of Science from inception to February 15, 2023. This systematic review followed Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines.
RESULTS
We identified a total of 620 studies. Only 41 were finally included in the meta-analysis. Most studies (61.0%) were from Brazil and Peru (14.6%). The total number of participants was 343,707. The pooled prevalence of HTLV-1/2 infection among CSA&C pregnant women was 1.30% (95% CI: 0.96-1.69) using anti-HTLV-1/2 antibody screening tests. There was a high heterogeneity (I = 98.6%). Confirmatory tests gave an HTLV-1 infection rate of 1.02% (95% CI: 0.75-1.33).
CONCLUSIONS
The prevalence of HTLV-1/2 infection among CSA&C pregnant women is 1.3%, most cases being HTLV-1. This rate is greater than for other microbial agents regularly checked as part of antenatal screening (such as HIV, hepatitis B, or syphilis). Thus, HTLV-1/2 antenatal testing should be mandatory among CSA&C pregnant women everywhere.
Topics: Humans; Pregnancy; Female; HTLV-I Infections; HTLV-II Infections; Prevalence; Caribbean Region; South America; Human T-lymphotropic virus 1; Pregnancy Complications, Infectious; Human T-lymphotropic virus 2; Central America
PubMed: 38522611
DOI: 10.1016/j.ijid.2024.107018 -
Proceedings of the National Academy of... Mar 2024Human retroviruses are derived from simian ones through cross-species transmission. These retroviruses are associated with little pathogenicity in their natural hosts,...
Human retroviruses are derived from simian ones through cross-species transmission. These retroviruses are associated with little pathogenicity in their natural hosts, but in humans, HIV causes AIDS, and human T-cell leukemia virus type 1 (HTLV-1) induces adult T-cell leukemia-lymphoma (ATL). We analyzed the proviral sequences of HTLV-1, HTLV-2, and simian T-cell leukemia virus type 1 (STLV-1) from Japanese macaques () and found that APOBEC3G (A3G) frequently generates G-to-A mutations in the HTLV-1 provirus, whereas such mutations are rare in the HTLV-2 and STLV-1 proviruses. Therefore, we investigated the mechanism of how HTLV-2 is resistant to human A3G (hA3G). HTLV-1, HTLV-2, and STLV-1 encode the so-called antisense proteins, HTLV-1 bZIP factor (HBZ), Antisense protein of HTLV-2 (APH-2), and STLV-1 bZIP factor (SBZ), respectively. APH-2 efficiently inhibits the deaminase activity of both hA3G and simian A3G (sA3G). HBZ and SBZ strongly suppress sA3G activity but only weakly inhibit hA3G, suggesting that HTLV-1 is incompletely adapted to humans. Unexpectedly, hA3G augments the activation of the transforming growth factor (TGF)-β/Smad pathway by HBZ, and this activation is associated with ATL cell proliferation by up-regulating and . In contrast, the combination of APH-2 and hA3G, or the combination of SBZ and sA3G, does not enhance the TGF-β/Smad pathway. Thus, HTLV-1 is vulnerable to hA3G but utilizes it to promote the proliferation of infected cells via the activation of the TGF-β/Smad pathway. Antisense factors in each virus, differently adapted to control host cellular functions through A3G, seem to dictate the pathogenesis.
Topics: Humans; Cell Line; Virulence; Human T-lymphotropic virus 1; Leukemia-Lymphoma, Adult T-Cell; Proviruses; Transforming Growth Factor beta; Basic-Leucine Zipper Transcription Factors; APOBEC-3G Deaminase
PubMed: 38502701
DOI: 10.1073/pnas.2309925121 -
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 -
Journal of Neurology Jun 2024Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic neurodegenerative disease. This multicenter,... (Randomized Controlled Trial)
Randomized Controlled Trial
Multicenter, randomized, double-blind, placebo-controlled phase 3 study of mogamulizumab with open-label extension study in a minimum number of patients with human T-cell leukemia virus type-1-associated myelopathy.
Human T-cell leukemia virus type 1 (HTLV-1)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a chronic neurodegenerative disease. This multicenter, randomized phase 3 study evaluated the efficacy and safety of 0.3 mg/kg intravenous mogamulizumab, a monoclonal antibody targeting-CC chemokine receptor 4, every 12 weeks in HAM/TSP patients. This study comprised a 24-week double-blind, placebo-controlled period, 24-week open-label period, and extension treatment period. The primary endpoint was the proportion of patients with a ≥ 1-grade improvement in the Osame motor disability score (OMDS). Secondary endpoints were changes in HTLV-1 proviral load, 10-m timed walk, cerebrospinal fluid (CSF) neopterin levels, and safety. The exploratory endpoint was CSF chemokine C-X-C motif ligand 10 (CXCL10) levels. Thirty-four and 33 patients were randomized to mogamulizumab and placebo arms, respectively. At the end of the double-blind period, no significant difference was found in the OMDS improvement rate or other secondary efficacy endpoints assessing motor activities. However, the mogamulizumab arm showed a significant decrease in HTLV-1 proviral load (- 59.39 ± 29.91% vs. placebo 2.32 ± 36.31%) and CSF neopterin (p < 0.001)/CXCL10 levels (p = 0.004). The baseline OMDS pattern and the 60-80% HTLV-1 proviral load reduction were sustained through the open-label and extension treatment periods. Although a higher incidence of rash (69.2%) was reported, the safety profile was similar compared with a previous phase 1/2a study. We found no significant difference in clinical benefit; however, mogamulizumab may provide long-term clinical benefit by preventing disease progression, as CSF neopterin/CXCL10 levels are associated with long-term prognosis in HAM/TSP.Clinical Trial Registration Number: NCT03191526 (registered date: 6-June-2017).
Topics: Humans; Double-Blind Method; Antibodies, Monoclonal, Humanized; Male; Middle Aged; Female; Paraparesis, Tropical Spastic; Adult; Aged; Neopterin; Human T-lymphotropic virus 1; Chemokine CXCL10; Viral Load; Treatment Outcome
PubMed: 38430272
DOI: 10.1007/s00415-024-12239-x -
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 -
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