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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 -
BMC Research Notes Jul 2023Human lymphotropic virus type 1 (HTLV-1) is the cause of two major diseases, ATLL and HAM/TSP in a percentage of carriers. Despite progress in understanding the...
The mirror like expression of genes involved in the FOXO signaling pathway could be effective in the pathogenesis of human lymphotropic virus type 1 (HTLV-1) through disruption of the downstream pathways.
OBJECTIVES
Human lymphotropic virus type 1 (HTLV-1) is the cause of two major diseases, ATLL and HAM/TSP in a percentage of carriers. Despite progress in understanding the pathogenesis of these two diseases, the exact pathogenesis mechanism is still not well understood. High-throughput technologies have revolutionized medical research. This study aims to investigate the mechanism of pathogenesis of these two diseases using the results of high-throughput analysis of microarray datasets.
RESULTS
A total of 100 differentially expressed genes were found between ATLL and HAM/TSP. After constructing protein-protein network and further analyzing, proteins including ATM, CD8, CXCR4, PIK3R1 and CD2 were found as the hub ones between ATLL and HAM/TSP. Finding the modules of the subnetwork revealed the enrichment of two common pathways including FOXO signaling pathway and Cell cycle with two common genes including ATM and CDKN2D. Unlike ATLL, ATM gene had higher expressions in HAM/TSP patients. The expression of CDKN2D was increased in ATLL patients. The results of this study could be helpful for understanding the pathogenic mechanism of these two diseases in the same signaling pathways.
Topics: Humans; Human T-lymphotropic virus 1; Paraparesis, Tropical Spastic; Leukemia-Lymphoma, Adult T-Cell; Microarray Analysis; Signal Transduction
PubMed: 37461070
DOI: 10.1186/s13104-023-06423-x -
International Journal of Molecular... Jun 2023Small RNAs (sRNAs) are epigenetic regulators of essential biological processes associated with the development and progression of leukemias, including adult T-cell...
Small RNAs (sRNAs) are epigenetic regulators of essential biological processes associated with the development and progression of leukemias, including adult T-cell leukemia/lymphoma (ATLL) caused by human T-cell lymphotropic virus type 1 (HTLV-1), an oncogenic human retrovirus originally discovered in a patient with adult T-cell leukemia/lymphoma. Here, we describe the sRNA profile of a 30-year-old woman with ATLL at the time of diagnosis and after maintenance therapy with the aim of correlating expression levels with response to therapy.
Topics: Adult; Female; Humans; Leukemia-Lymphoma, Adult T-Cell; Human T-lymphotropic virus 1; RNA; Lymphoma
PubMed: 37445821
DOI: 10.3390/ijms241310643 -
Virulence Dec 2023Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropic spastic paraparesis (HAM/TSP) is an insidiously progressive spinal cord disease for which...
Human T-cell lymphotropic virus type 1 (HTLV-1)-associated myelopathy/tropic spastic paraparesis (HAM/TSP) is an insidiously progressive spinal cord disease for which there is no effective treatment. There is great interest in developing potential biomarkers to predict the pathogenesis of HAM/TSP disease. In this study, Illumina Massive Parallel Sequencing (MPS) technology was used to investigate the cellular global noncoding RNAome expression profile in HAM/TSP patients ( = 10), asymptomatic HTLV-1-infected carriers (ASP, = 8), and a second group of healthy controls ( = 5). Various bioinformatics tools were used to align, annotate, and profile the sRNA-MPS reads. Among the 402 sRNAs detected, 251 were known and 50 were potentially novel sRNAs in the HAM and ASP groups compared with the HC group. Sixty-eight known sRNAs were significantly different between the ASP and HAM groups. Eighty-eight mature miRNAs were downregulated in subjects from HAM compared with ASP. Three of these miRs (hsa-miR-185-5p, 32-5p, and 192-5p) have the potential to be used as biomarkers for predicting the pathogenesis of HAM/TSP. The seven most deregulated miRs target genes have been associated with a variety of biological processes and molecular functions. The reactome pathways relevant to our findings provide a rich source of data and offer the opportunity to better understand sRNA regulation and function in HTLV-1 pathophysiology. To the best of our knowledge, this study is the first to demonstrate evaluates sRNAs in HTLV-1 patients with HAM/TSP.
Topics: Humans; Prognosis; Paraparesis, Tropical Spastic; Human T-lymphotropic virus 1; MicroRNAs; Biomarkers
PubMed: 37394816
DOI: 10.1080/21505594.2023.2230015 -
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 -
BMC Infectious Diseases Jun 2023In vitro diagnostics (IVDs) for primary detection test/screening of human T-cell leukemia virus (HTLV) have recently been updated to new-generation products in Japan. In...
BACKGROUND
In vitro diagnostics (IVDs) for primary detection test/screening of human T-cell leukemia virus (HTLV) have recently been updated to new-generation products in Japan. In this study, the performance of these products was evaluated and discussed in terms of the usability of HTLV diagnosis in Japan.
METHODS
The performance of 10 HTLV IVDs for primary detection test and confirmatory/discriminatory test was evaluated. Plasma specimens that had been declared ineligible for transfusion were provided by the Japanese Red Cross Blood Center.
RESULTS
The diagnostic specificity of the IVDs was 100% (160/160). Six sandwich assays resulted in all HTLV-1/HTLV-positive specimens being positive (46/46). On the other hand, one sandwich assay, IVD under development 2 (UD2), resulted in one HTLV-1-positive and one HTLV-positive specimen being negative (44/46, 95.7%). One indirect assay, HISCL HTLV-1, could not detect one HTLV-positive specimen (45/46, 97.8%), but the updated product, UD1, correctly detected it (46/46, 100%). Serodia HTLV-I, based on a particle agglutination assay, resulted in 44 of the 46 positive specimens, but could not detect two specimens (44/46, 95.7%). ESPLINE HTLV-I/II, based on an immunochromatography assay (ICA), was able to diagnose all specimens as positive (46/46, 100%).
CONCLUSIONS
Six sandwich assays and an ICA demonstrated high diagnostic sensitivity and specificity and are recommended for use in HTLV diagnosis in conjunction with confirmatory/discriminatory test using the INNO-LIA HTLV-I/II Score.
Topics: Humans; HTLV-I Infections; Japan; Human T-lymphotropic virus 1; Human T-lymphotropic virus 2; Leukemia, T-Cell
PubMed: 37340346
DOI: 10.1186/s12879-023-08402-w -
PLoS Pathogens Jun 2023Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic cause of adult T-cell leukemia/lymphoma (ATL) and encodes a viral oncoprotein (Hbz) that is consistently...
Human T-cell leukemia virus type 1 (HTLV-1) is the etiologic cause of adult T-cell leukemia/lymphoma (ATL) and encodes a viral oncoprotein (Hbz) that is consistently expressed in asymptomatic carriers and ATL patients, suggesting its importance in the development and maintenance of HTLV-1 leukemic cells. Our previous work found Hbz protein is dispensable for virus-mediated T-cell immortalization but enhances viral persistence. We and others have also shown that hbz mRNA promotes T-cell proliferation. In our current studies, we evaluated the role of hbz mRNA on HTLV-1-mediated immortalization in vitro as well as in vivo persistence and disease development. We generated mutant proviral clones to examine the individual contributions of hbz mRNA, hbz mRNA secondary structure (stem-loop), and Hbz protein. Wild-type (WT) and all mutant viruses produced virions and immortalized T-cells in vitro. Viral persistence and disease development were also evaluated in vivo by infection of a rabbit model and humanized immune system (HIS) mice, respectively. Proviral load and sense and antisense viral gene expression were significantly lower in rabbits infected with mutant viruses lacking Hbz protein compared to WT or virus with an altered hbz mRNA stem-loop (M3 mutant). HIS mice infected with Hbz protein-deficient viruses showed significantly increased survival times compared to animals infected with WT or M3 mutant virus. Altered hbz mRNA secondary structure, or loss of hbz mRNA or protein, has no significant effect on T-cell immortalization induced by HTLV-1 in vitro; however, the Hbz protein plays a critical role in establishing viral persistence and leukemogenesis in vivo.
Topics: Humans; Mice; Rabbits; Animals; Human T-lymphotropic virus 1; RNA, Messenger; Retroviridae Proteins; Basic-Leucine Zipper Transcription Factors; Viral Proteins; Leukemia-Lymphoma, Adult T-Cell; Cell Line; Proviruses
PubMed: 37327244
DOI: 10.1371/journal.ppat.1011459 -
Frontiers in Cellular and Infection... 2023Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus known to cause two major diseases: adult T-cell leukemia/lymphoma and a progressive neuromyelopathy-tropical...
BACKGROUND
Human T-cell leukemia virus type 1 (HTLV-1) is a retrovirus known to cause two major diseases: adult T-cell leukemia/lymphoma and a progressive neuromyelopathy-tropical spastic paraparesis. Many viruses may be involved in the pathogenesis of thyroiditis; however, few studies have focused on the role of HTLV-1. We aimed to investigate the association between HTLV-1 and biological thyroid dysfunction.
METHODS
We included 357 patients with a positive HTLV-1 serology and thyroid-stimulating hormone assay data between 2012 and 2021 in a hospital in French Guiana; we compared the prevalence of hypothyroidism and hyperthyroidism in this group with that in an HTLV-1-negative control group (722 persons) matched for sex and age.
RESULTS
The prevalence of hypothyroidism and hyperthyroidism in patients with HTLV-1 infection was significantly higher than that in the control group (11% versus 3.2% and 11.3% versus 2.3%, respectively; < 0.001).
CONCLUSION
Our study shows, for the first time, the association between HTLV-1 and dysthyroidism in a large sample, suggesting that thyroid function exploration should be systematically implemented in this population as this may have an impact on therapeutic management.
Topics: Adult; Humans; Human T-lymphotropic virus 1; Hyperthyroidism; Hypothyroidism; Leukemia-Lymphoma, Adult T-Cell; Male; Female; Adolescent; Young Adult; Middle Aged; Aged; Case-Control Studies; French Guiana; Prevalence
PubMed: 37293205
DOI: 10.3389/fcimb.2023.1164526 -
Virology Journal Jun 2023ATLL (Adult T-Cell Leukemia/Lymphoma) is an aggressive hematological malignancy. This T-cell non-Hodgkin lymphoma, caused by the human T-cell leukemia virus type 1... (Meta-Analysis)
Meta-Analysis
BACKGROUND
ATLL (Adult T-Cell Leukemia/Lymphoma) is an aggressive hematological malignancy. This T-cell non-Hodgkin lymphoma, caused by the human T-cell leukemia virus type 1 (HTLV-1), is challenging to treat. There is no known treatment for ATLL as of yet. However, it is recommended to use Zidovudine and Interferon Alfa-based regimens (AZT/IFN), chemotherapy, and stem cell transplant. This study aims to review the outcome of patients with different subtypes of ATLL treated with Zidovudine and Interferon Alfa-based regimens.
METHODS
A systematic search was carried out for articles evaluating outcomes of ATLL treatment by AZT/IFN agents on human subjects from January 1, 2004, until July 1, 2022. Researchers assessed all studies regarding the topic, followed by extracting the data. A random-effects model was used in the meta-analyses.
RESULTS
We obtained fifteen articles on the AZT/IFN treatment of 1101 ATLL patients. The response rate of the AZT/IFN regimen yielded an OR of 67% [95% CI: 0.50; 0.80], a CR of 33% [95% CI: 0.24; 0.44], and a PR of 31% [95% CI: 0.24; 0.39] among individuals who received this regimen at any point during their treatment. Our subgroup analyses' findings demonstrated that patients who received front-line and combined AZT/IFN therapy responded better than those who received AZT/IFN alone. It is significant to note that patients with indolent subtypes of disease had considerably higher response rates than individuals with aggressive disease.
CONCLUSION
IFN/AZT combined with chemotherapy regimens is an effective treatment for ATLL patients, and its use in the early stages of the disease may result in a greater response rate.
Topics: Adult; Humans; Zidovudine; Interferon-alpha; Leukemia-Lymphoma, Adult T-Cell; Human T-lymphotropic virus 1; Lymphoma
PubMed: 37287047
DOI: 10.1186/s12985-023-02077-0 -
Archives of Razi Institute Dec 2022The human papillomavirus (HPV) is a crucial but not the predominant cause of cervical cancer. This study aimed to identify gene expression in human papillomavirus using...
The human papillomavirus (HPV) is a crucial but not the predominant cause of cervical cancer. This study aimed to identify gene expression in human papillomavirus using a pap smear. A total of 120 serum samples, 60 samples were taken from infected females with papillomavirus and another 60 as healthy control. These samples were collected after pap smears were done. These women attended Al-Emam Hospital for delivery from March 1st, 2021, to February 28th, 2022. The levels of Pap-IgM and Pap-IgG were increasing among patients attacked by papilloma. The levels of viruses were higher than in levels than control groups, which was indicated by increases in the scores of mean and standard deviation (2.01±1.17, 0.11±0.02), (14.24±7.10, 0.4±0.17), respectively. Statistically, these differences between the levels of the studied groups were highly significant. The levels of the three markers Ca19.9, Ca125, and Ca15.3 were normal in levels among papilloma patients and the control group compared to the normal value of the three markers, which equaled N.V. (>37ng/ml). Statistically, these differences between the scores of the three markers, which were measured depending on mean and standard deviation, were highly significant. There is a low positive correlation between the levels of Pap-IgM (>1) with levels of Ca19.9 (>37) with (r=0.409**, =0.000), while there is a moderate association between the levels of Pap-IgM (>1) with Ca125 (>35ng/ml) and Ca15.3 (>37ng/ml) levels with (r=0.574**, 0.565**, =0.000, 0.000) respectively. Also, this table documents that there is a moderate positive correlation between the levels of Pap-IgG (>1) and the levels of the three tumor markers Ca19.9 (>37), Ca125 (>35), and Ca15.3 (>37) (r=0.521**, 0.592**, 0.647**). The gene expression was investigated in patients infected with Papillomaviruses compared to healthy controls using real-time PCR. The results showed a high Ct value for patients and controls with a high Ct value of templates, preoperational to the gene concentration.
Topics: Female; Humans; Human papillomavirus 16; Human Papillomavirus Viruses; Human T-lymphotropic virus 1; Immunoglobulin G; Immunoglobulin M; Papanicolaou Test; Papilloma; Papillomaviridae; Papillomavirus Infections; Vaginal Smears
PubMed: 37274879
DOI: 10.22092/ARI.2022.359292.2397