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Multiple Sclerosis and Related Disorders Jul 2024The roles of endocannabinoids are described in immune modulation and neuroprotection. HTLV-1-associated myelopathy (HAM/TSP) is an inflammatory neurodegenerative...
BACKGROUND/AIM
The roles of endocannabinoids are described in immune modulation and neuroprotection. HTLV-1-associated myelopathy (HAM/TSP) is an inflammatory neurodegenerative disease. Therefore, in this study, the interactions of HTLV-1 regulatory factors and host cannabinoid receptors (CBRs) were evaluated in HAM/TSP.
METHODS
Nineteen HAM/TSPs, 22 asymptomatic carriers (ACs), and 18 healthy controls (HCs) were enrolled. RNA was extracted from PBMCs and then reverse-transcribed to cDNA. The gene expression of CB1R and CB2R, as well as HTLV-1 proviral load (PVL), Tax and HTLV-1 basic leucine zipper factor (HBZ) were assessed by RT-qPCR.
RESULTS
The mean expression of CB1R in ACs (8.51 ± 2.76) was significantly higher than HAMTSPs (1.593 ± 0.74, p = 0.05) and also HCs (0.10 ± 0.039, p = 0.001). The CB2R gene expression level in ACs (2.62±0.44) was significantly higher than HAM/TSPs (0.59 ± 0.15, p = 0.001) and HCs (1.00 ± 0.2, p = 0.006). Meanwhile there was a strong correlation between CB1R and CB2R gene expression levels in the HCs and HAM/TSPs (p = 0.001). HTLV-1-Tax expression in HAM/TSPs (386 ± 104) was higher than ACs (75 ± 32) and statistically significant (p = 0.003). While HTLV-1-HBZ was only expressed in three AC subjects and five HAM/TSPs, thus it cannot be analyzed.
CONCLUSION
The up-regulation of CB2R has immunomodulatory effects in inflammatory reactions. While CB1R as a neuroprotective agent may suppress inflammatory reactions in ACs, preventing HAM/TSP. It seems that, like multiple sclerosis (MS), cannabinoid medications are beneficial in HAM/TSP.
Topics: Humans; Male; Female; Receptor, Cannabinoid, CB1; Adult; Receptor, Cannabinoid, CB2; Paraparesis, Tropical Spastic; Middle Aged; Human T-lymphotropic virus 1; Gene Products, tax; Basic-Leucine Zipper Transcription Factors; Viral Load; Retroviridae Proteins
PubMed: 38704874
DOI: 10.1016/j.msard.2024.105659 -
International Journal of Infectious... Aug 2024Infective dermatitis associated with human T-cell lymphotropic virus type-1 (HTLV-1) (IDH) is a severe form of chronically infected eczema occurring in early childhood,... (Review)
Review
Infective dermatitis associated with human T-cell lymphotropic virus type-1 (HTLV-1) (IDH) is a severe form of chronically infected eczema occurring in early childhood, although very rarely cases have been reported in adults. Most of the cases are from Jamaica and Brazil and occur in individuals with low socioeconomic status. IDH is always associated with refractory Staphylococcus aureus or beta-hemolytic Streptococcus infection of the skin and nasal vestibules. Patients with IDH may develop other even more severe HTLV-1-associated diseases, such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) of early or late appearance and adult T-cell leukemia/lymphoma. In the context of the Brazilian experience, it has been observed that 54% of IDH patients exhibit the juvenile form of HAM/TSP while the estimated incidence of adult HAM/TSP is 3%. As there are no curative treatments for HTLV-1 infection (or vaccines) or most of its associated diseases, prevention of infection is fundamental, mainly by vertical transmission, as it is responsible for the development of IDH, infantojuvenile HAM/TSP, and ATL. Public measures to reduce this transmission must be implemented urgently. Furthermore, it is recommended, mainly in HTLV-1 endemic areas, to search for HTLV-1 infection in all patients with infected eczema, even in adults.
Topics: Humans; HTLV-I Infections; Human T-lymphotropic virus 1; Brazil; Paraparesis, Tropical Spastic; Adult; Dermatitis
PubMed: 38697604
DOI: 10.1016/j.ijid.2024.107058 -
The Canadian Veterinary Journal = La... May 2024The primary objective was to determine the youngest age group where bovine leukemia virus (BLV)-infected dairy animals were identified. The secondary objective was to...
OBJECTIVE
The primary objective was to determine the youngest age group where bovine leukemia virus (BLV)-infected dairy animals were identified. The secondary objective was to investigate associations between age-specific management practices and BLV infection status of different age groups of dairy calves and heifers.
PROCEDURE
For enrolled herds, BLV status was determined using blood samples from pre-weaned calves, weaned calves, and breeding-age heifers; and bulk tank milk from the adult herd. A questionnaire investigating age-specific management factors was administered for each herd. Ordinal logistic regression was performed to identify management factors associated with the youngest age range in which BLV was identified.
RESULTS
Fifty-three dairy herds from the 4 provinces in Atlantic Canada were enrolled. Bovine leukemia virus was most commonly earliest identified in pre-weaned heifers (18 herds, 32.1%) and the adult herd (18 herds, 32.1%). Ordinal logistic regression revealed that BLV was first identified in older age groups more often than in younger age groups when herds regrouped weaned heifers at least once, when fly control was used for breeding-age heifers, when herds practiced foot trimming on breeding-age heifers, and when bred heifers were brought in.
CONCLUSION
Producers can use results to identify the youngest age group(s) in which BLV is identified and to tailor management strategies to prevent new infections.
Topics: Animals; Cattle; Leukemia Virus, Bovine; Female; Enzootic Bovine Leukosis; Dairying; Canada; Age Factors; Milk; Surveys and Questionnaires
PubMed: 38694741
DOI: No ID Found -
Frontiers in Immunology 2024Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma. The HTLV-1 Tax constitutively activates nuclear factor-κB...
Human T-cell leukemia virus type 1 (HTLV-1) is the etiological agent of adult T-cell leukemia/lymphoma. The HTLV-1 Tax constitutively activates nuclear factor-κB (NF-κB) to promote the survival and transformation of HTLV-1-infected T cells. Despite extensive study of Tax, how Tax interacts with host factors to regulate NF-κB activation and HTLV-1-driven cell proliferation is not entirely clear. Here, we showed that overexpression of Poly (rC)-binding protein 1 (PCBP1) promoted Tax-mediated IκB kinase (IKK)-NF-κB signaling activation, whereas knockdown of PCBP1 attenuated Tax-dependent IKK-NF-κB activation. However, Tax activation of HTLV-1 long terminal repeat was unaffected by PCBP1. Furthermore, depletion of PCBP1 led to apoptosis and reduced proliferation of HTLV-1-transformed cells. Mechanistically, PCBP1 interacted and co-localized with Tax in the cytoplasm, and PCBP1 KH3 domain was indispensable for the interaction between PCBP1 and Tax. Moreover, PCBP1 facilitated the assembly of Tax/IKK complex. Collectively, our results demonstrated that PCBP1 may exert an essential effect in Tax/IKK complex combination and subsequent NF-κB activation, which provides a novel insight into the pathogenetic mechanisms of HTLV-1.
Topics: Humans; Gene Products, tax; NF-kappa B; Human T-lymphotropic virus 1; RNA-Binding Proteins; DNA-Binding Proteins; Heterogeneous-Nuclear Ribonucleoproteins; Signal Transduction; HEK293 Cells; Protein Binding; Cell Proliferation; HTLV-I Infections; Apoptosis; I-kappa B Kinase; Host-Pathogen Interactions
PubMed: 38690287
DOI: 10.3389/fimmu.2024.1375168 -
BMJ Case Reports Apr 2024A middle-aged man with progressive multifocal leukoencephalopathy (PML) in a human T-cell lymphotropic virus type-1 (HTLV-1) carrier on haemodialysis presented with mild...
A middle-aged man with progressive multifocal leukoencephalopathy (PML) in a human T-cell lymphotropic virus type-1 (HTLV-1) carrier on haemodialysis presented with mild dysarthria and ataxia. Brain MRI revealed asymmetric T-hyperintense lesions in the cerebral white matter, cerebellum and brainstem. A small amount of JC virus (JCV) genome in cerebrospinal fluid was detected by PCR and cerebellar biopsy demonstrated JCV-DNA presence. Pathological findings showed demyelinating lesions and glial cells with mildly enlarged nuclei, accompanied by T-lymphocytes, neutrophils and plasma cell infiltration. The CD4+/CD8+ratio was 0.83. High-dose corticosteroid therapy was effective for inflammatory PML lesions, and the administration of mefloquine combined with mirtazapine led to favourable outcome. The encephalitis in this case is considered to have occurred secondarily to JCV infection in the presence of HTLV-1 infection. Therefore, it is crucial to investigate the presence of HTLV-1 in order to understand the aetiology of this brain inflammation.
Topics: Humans; Leukoencephalopathy, Progressive Multifocal; Male; HTLV-I Infections; Middle Aged; Human T-lymphotropic virus 1; JC Virus; Coinfection; Mirtazapine; Magnetic Resonance Imaging; Mefloquine
PubMed: 38688573
DOI: 10.1136/bcr-2023-257805 -
The Journal of Veterinary Medical... Jun 2024The present study analyzed B-cell clonality and bovine leukemia virus (BLV) provirus integration sites in cattle with enzootic bovine leukosis (EBL) having BLV proviral...
The present study analyzed B-cell clonality and bovine leukemia virus (BLV) provirus integration sites in cattle with enzootic bovine leukosis (EBL) having BLV proviral copy numbers less or greater than the number of bovine nucleated cells. EBL cattle with BLV copy numbers less than the number of bovine nucleated cells showed monoclonal and biclonal proliferation of B-cells with one BLV provirus integration site. On the other hand, EBL cattle with BLV copy numbers greater than the number of bovine nucleated cells showed monoclonal proliferation of B-cells with two BLV provirus integration sites. These results suggest that superinfection of BLV can occur in EBL cattle.
Topics: Animals; Leukemia Virus, Bovine; Enzootic Bovine Leukosis; Cattle; Proviruses; DNA, Viral; B-Lymphocytes; Virus Integration; Cell Proliferation
PubMed: 38631888
DOI: 10.1292/jvms.24-0037 -
International Journal of Biological... May 2024Infection with bovine leukemia virus (BLV) leads to enzootic bovine leukosis, the most prevalent neoplastic disease in cattle. Due to the lack of commercially available...
Infection with bovine leukemia virus (BLV) leads to enzootic bovine leukosis, the most prevalent neoplastic disease in cattle. Due to the lack of commercially available vaccines, reliable eradication of the disease can be achieved through the testing and elimination of BLV antibody-positive animals. In this study, we developed a novel competitive ELISA (cELISA) to detect antibodies against BLV capsid protein p24. Recombinant p24 protein expressed by Escherichia coli, in combination with the monoclonal antibody 2G11 exhibiting exceptional performance, was used for the establishment of the cELISA. Receiver-operating characteristic curve analysis showed that the sensitivity and specificity of the assay were 98.85 % and 98.13 %, respectively. Furthermore, the established cELISA was specific for detecting BLV-specific antibodies, without cross-reactivity to antisera for six other bovine viruses. Significantly, experimental infection of cattle and sheep with BLV revealed that the cELISA accurately monitors seroconversion. In a performance evaluation, the established cELISA displayed a high agreement with Western blotting and the commercial BLV gp51 cELISA kit in the detection of 242 clinical samples, respectively. In conclusion, the novel p24 cELISA exhibited the potential to be a reliable and efficient diagnostic tool for BLV serological detection with a broad application prospect.
Topics: Leukemia Virus, Bovine; Animals; Enzyme-Linked Immunosorbent Assay; Cattle; Antibodies, Viral; Antibodies, Monoclonal; Enzootic Bovine Leukosis; Capsid Proteins; Sensitivity and Specificity; Recombinant Proteins; ROC Curve
PubMed: 38621561
DOI: 10.1016/j.ijbiomac.2024.131446 -
Nature Microbiology Apr 2024
Topics: Human T-lymphotropic virus 1; Humans; HTLV-I Infections
PubMed: 38575706
DOI: 10.1038/s41564-024-01652-7 -
European Journal of Haematology Jul 2024We aimed to determine the role of dihydroorotate dehydrogenase (DHODH) in pathogenesis of adult T-cell leukemia (ATL) caused by human T-cell leukemia virus type 1...
OBJECTIVES
We aimed to determine the role of dihydroorotate dehydrogenase (DHODH) in pathogenesis of adult T-cell leukemia (ATL) caused by human T-cell leukemia virus type 1 (HTLV-1) and the effects of its inhibition on the de novo pyrimidine biosynthesis pathway.
METHODS
Cell proliferation, viability, cycle, and apoptosis were analyzed using WST-8 assays, flow cytometry, and Hoechst 33342 staining. To elucidate the molecular mechanisms involved in the anti-ATL effects of DHODH knockdown and inhibition, RT-PCR and immunoblotting were conducted.
RESULTS
HTLV-1-infected T-cell lines aberrantly expressed DHODH. Viral infection and the oncoprotein, Tax, enhanced DHODH expression, while knockdown of DHODH decreased HTLV-1-infected T-cell growth. In addition, BAY2402234, a DHODH inhibitor, exerted an anti-proliferative effect, which was reversed by uridine supplementation. BAY2402234 induced DNA damage and S phase arrest by downregulating c-Myc, CDK2, and cyclin A and upregulating p53 and cyclin E. It also induced caspase-mediated apoptosis by the upregulation of pro-apoptotic and downregulation of anti-apoptotic proteins. Furthermore, BAY2402234 induced caspase-independent ferroptosis and necroptosis. It decreased phosphorylation of IKK, IκBα, PTEN, Akt, and its downstream targets, suggesting that inhibition of NF-κB and Akt signaling is involved in its anti-ATL action.
CONCLUSION
These findings highlight DHODH as a potential therapeutic target for treating ATL.
Topics: Humans; Dihydroorotate Dehydrogenase; Leukemia-Lymphoma, Adult T-Cell; Oxidoreductases Acting on CH-CH Group Donors; Cell Proliferation; Apoptosis; Human T-lymphotropic virus 1; Cell Line, Tumor; Signal Transduction; Molecular Targeted Therapy; Pyrimidines; Gene Knockdown Techniques; Cell Survival; Cell Cycle; NF-kappa B
PubMed: 38558052
DOI: 10.1111/ejh.14209 -
International Journal of Molecular... Mar 2024Human T-cell leukemia virus type 1 (HTLV-1), a virus that affects 5-10 million people globally, causes several diseases, including adult T-cell leukemia-lymphoma and...
Human T-cell leukemia virus type 1 (HTLV-1), a virus that affects 5-10 million people globally, causes several diseases, including adult T-cell leukemia-lymphoma and HTLV-1-associated uveitis (HU). HU is prevalent in Japan and often leads to secondary glaucoma, which is a serious complication. We investigated the efficacy of ripasudil, a Rho-associated coiled coil-forming protein kinase inhibitor, in alleviating changes in human trabecular meshwork cells (hTM cells) infected with HTLV-1. HTLV-1-infected hTM cells were modeled in vitro using MT-2 cells, followed by treatment with varying concentrations of ripasudil. We assessed changes in cell morphology, viability, and inflammatory cytokine levels, as well as NF-κB activation. The results showed that ripasudil treatment changed the cell morphology, reduced the distribution of F-actin and fibronectin, and decreased the levels of certain inflammatory cytokines, such as interleukin (IL)-6, IL-8, and IL-12. However, ripasudil did not significantly affect NF-κB activation or overall cell viability. These findings suggest that ripasudil has the potential to treat secondary glaucoma in patients with HU by modulating cytoskeletal organization and alleviating inflammation in HTLV-1-infected hTM cells. This study lays the foundation for further clinical studies exploring the effectiveness of ripasudil for the treatment of secondary glaucoma associated with HU.
Topics: Adult; Humans; Human T-lymphotropic virus 1; NF-kappa B; Glaucoma; Uveitis; Cytokines; Interleukin-6; rho-Associated Kinases; Isoquinolines; Sulfonamides
PubMed: 38542203
DOI: 10.3390/ijms25063229