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Veterinarni Medicina Oct 2023Enzootic bovine leucosis is caused by bovine leukaemia virus (BLV), a belonging to the family . BLV causes huge economic losses to the dairy industry in the form...
Enzootic bovine leucosis is caused by bovine leukaemia virus (BLV), a belonging to the family . BLV causes huge economic losses to the dairy industry in the form of decreased milk production, premature culling, and poor reproductive performance of the animals. The aim of the present study was to determine the seroprevalence of BLV infection in buffalo in two districts of Punjab, Pakistan. A total of 384 samples were collected and analysed using a commercial indirect enzyme-linked immunosorbent assay (ELISA) to investigate the seroprevalence of BLV through the detection of the anti-BLV gp51 antibody. A predesigned data questionnaire proforma was employed to find out the association of risk factors with disease. Overall, 18.2% of buffaloes were seropositive for BLV in the study population. The results revealed a significant association ( < 0.05) of age with BLV infection. Furthermore, milk yield and pregnancy had a significant association with the seroprevalence of BLV infection in buffalo whereas no significant association was found with sex, breeding, and health status. Biochemical and oxidative stress markers revealed a significant decrease in liver enzymes alanine transaminase (ALT) and aspartate transaminase (AST), glutathione peroxidase (GPX), and superoxide dismutase (SOD) in seropositive animals as compared to healthy animals. It is concluded that BLV has a considerable prevalence in buffalo in Punjab, Pakistan and there is a dire need to investigate the disease epidemiology at both national and international levels and strategies should be developed to implement an effective control program.
PubMed: 38028205
DOI: 10.17221/57/2023-VETMED -
BioRxiv : the Preprint Server For... Jul 2023Human T-cell leukemia virus type 1 (HTLV-1) has an atypical immature particle morphology compared to other retroviruses. This indicates that these particles are formed...
Human T-cell leukemia virus type 1 (HTLV-1) has an atypical immature particle morphology compared to other retroviruses. This indicates that these particles are formed in a way that is unique. Here we report the results of cryo-electron tomography (cryo-ET) studies of HTLV-1 virus-like particles (VLPs) assembled , as well as derived from cells. This work shows that HTLV-1 employs an unconventional mechanism of Gag-Gag interactions to form the immature viral lattice. Analysis of high-resolution structural information from immature CA tubular arrays reveals that the primary stabilizing component in HTLV-1 is CA-NTD. Mutagenesis and biophysical analysis support this observation. This distinguishes HTLV-1 from other retroviruses, in which the stabilization is provided primarily by the CA-CTD. These results are the first to provide structural details of the quaternary arrangement of Gag for an immature deltaretrovirus, and this helps explain why HTLV-1 particles are morphologically distinct.
PubMed: 37546793
DOI: 10.1101/2023.07.24.548988 -
Transfusion Medicine (Oxford, England) Aug 2023This study evaluated the Human T-lymphotropic virus (HTLV) screening policy impact on the HTLV seroprevalence from 2009 to 2018 as well as the differences between...
OBJECTIVES
This study evaluated the Human T-lymphotropic virus (HTLV) screening policy impact on the HTLV seroprevalence from 2009 to 2018 as well as the differences between administrative districts in terms of prevalence distribution in Taiwan.
BACKGROUND
Since February 1996, the Taiwan Blood Services Foundation (TBSF) had conducted HTLV screening of blood donors. The HTLV seroprevalence was 0.032% in 1999.
MATERIALS AND METHODS
This cross-sectional study included donors' data collected from blood donation centres across Taiwan from 2009 to 2018. Enzyme immunoassay and Western blot assay were used for screening and confirmation of HTLV infections. In this study, the researchers calculated the trends in the HTLV rates of first-time and repeat donors across time as well as the HTLV prevalence distribution across the 22 administrative districts of Taiwan.
RESULTS
Amongst 17 977 429 employed blood donations, 739 HTLV-seropositive donations (4.11 per 100 000 donations) were identified. The HTLV-positive donors were aged between 17 and 64 years, with a median age of 49 years. The overall seropositivity rates of first-time and repeat donors were 34.36/100 000 and 1.27/100 000. HTLV seroprevalence in first-time blood donors significantly decreased by 57% (crude odds ratio [95% confidence interval] (crude OR [95% CI]) = 0.43 [0.28-0.64]) within 10 years. A slight decline was also identified in repeat donors (crude OR [95% CI] = 0.73 [0.4-1.32]). Donors from different districts showed significantly varied prevalence. Most districts with high prevalence are situated in eastern Taiwan, for both donation types. Older blood donors were more likely to be infected with HTLV than younger ones in first time and repeat donors. Middle age donors (50-65 years) had an 18.47-39.65 greater risk than those aged <20 years. Significant higher risk of female was observed in both donation types. Amongst different age groups, first-time female donors increase 1.31-1.88 times infection risk and female in repeat donor group had 1.55-3.43 times greater risk.
CONCLUSION
Over years of implementation of the HTLV blood donor screening policy by the TBSF, the HTLV seroprevalence of first-time donors has decreased consistently. Moreover, the HTLV seroprevalence of repeat donors has dropped considerably. This implies that the screening policy provides continued benefit. Females and older blood donors were more likely infected with HTLV than males and younger blood donors. The influence of age on infection was greater amongst first-time donors than amongst repeat donors. Therefore, appropriate measures should be taken to ensure public safety.
Topics: Middle Aged; Male; Humans; Female; Adolescent; Young Adult; Adult; Human T-lymphotropic virus 1; HTLV-I Infections; Blood Donors; Seroepidemiologic Studies; Cross-Sectional Studies; Follow-Up Studies; HTLV-II Infections; Human T-lymphotropic virus 2
PubMed: 37209036
DOI: 10.1111/tme.12979 -
Journal of Dairy Science Dec 2023Bovine leukemia virus (BLV) has spread worldwide and causes serious problems in the cattle industry owing to the lack of effective treatments and vaccines. Bovine...
Effectiveness of integrated bovine leukemia virus eradication strategies utilizing cattle carrying resistant and susceptible major histocompatibility complex class II DRB3 alleles.
Bovine leukemia virus (BLV) has spread worldwide and causes serious problems in the cattle industry owing to the lack of effective treatments and vaccines. Bovine leukemia virus is transmitted via horizontal and vertical infection, and cattle with high BLV proviral load (PVL), which is a useful index for estimating disease progression and transmission risk, are considered major infectious sources within herds. The PVL strongly correlates with highly polymorphic bovine lymphocyte antigen (BoLA)-DRB3 alleles. The BoLA-DRB3*015:01 and *012:01 alleles are known susceptibility-associated markers related to high PVL, and cattle with susceptible alleles may be at a high risk of BLV transmission via direct contact with healthy cows. In contrast, the BoLA-DRB3*009:02 and *014:01:01 alleles comprise resistant markers associated with the development of low PVL, and cattle with resistant alleles may be low-risk spreaders for BLV transmission and disrupt the BLV transmission chain. However, whether polymorphisms in BoLA-DRB3 are useful for BLV eradication in farms remains unknown. Here, we conducted a validation trial of the integrated BLV eradication strategy to prevent new infection by resistant cattle and actively eliminate susceptible cattle in addition to conventional BLV eradication strategies to maximally reduce the BLV prevalence and PVL using a total of 342 cattle at 4 stall-barn farms in Japan from 2017 to 2019. First, we placed the resistant milking cattle between the BLV-positive and BLV-negative milking cattle in a stall barn for 3 yr. Interestingly, the resistant cattle proved to be an effective biological barrier to successfully block the new BLV infections in the stall-barn system among all 4 farms. Concomitantly, we actively eliminated cattle with high PVL, especially susceptible cattle. Indeed, 39 of the 60 susceptible cattle (65%), 76 of the 140 neutral cattle (54%), and 20 of the 41 resistant cattle (48.8%) were culled on 4 farms for 3 years. Consequently, BLV prevalence and mean PVL decreased in all 4 farms. In particular, one farm achieved BLV-free status in May 2020. By decreasing the number of BLV-positive animals, the revenue-enhancing effect was estimated to be ¥5,839,262 ($39,292.39) for the 4 farms over 3 yr. Our results suggest that an integrated BLV eradication program utilization of resistant cattle as a biological barrier and the preferential elimination of susceptible cattle are useful for BLV infection control.
Topics: Animals; Cattle; Female; Alleles; Cattle Diseases; Disease Susceptibility; Enzootic Bovine Leukosis; Histocompatibility Antigens Class II; Leukemia Virus, Bovine; Major Histocompatibility Complex
PubMed: 37641252
DOI: 10.3168/jds.2023-23524 -
Journal of Inorganic Biochemistry Aug 2023Chalcone and thiosemicarbazone have attracted attention due to their easy synthetic procedure and high success in the development of antiviral and antitumor, however,...
Chalcone and thiosemicarbazone have attracted attention due to their easy synthetic procedure and high success in the development of antiviral and antitumor, however, there are few biological data on the evaluation of chalcone-thiosemicarbazone hybrids and their complexation with metal ions. In this sense, the present work reports the synthesis and characterization of the hybrid (Z)-2-((E)-3-(4-chlorophenyl)-1-phenylallylidene)hydrazine-1-carbothioamide (CTCl) and its Zn(II)-complex (CTCl-Zn). The compounds were cell-based evaluated in terms of cytotoxicity against human T-cell lymphotropic virus type 1 (HTLV-1) infected leukemia cells (MT-2) and the experimental data were correlated with molecular docking calculations. The ligand and Zn(II)-complex were easily synthesized with a good yield - 57% and 79%, respectively. The dynamic of E/Z isomers with respect to the imine bond configuration of CTCl was evidenced by H NMR experiments in DMSO‑d, while the X-ray diffraction of CTCl-Zn showed that Zn(II) ion is tetracoordinated to two ligands in a bidentate mode and the metal ion lies on an intermediate geometry between the see-saw and trigonal pyramid. The ligand and complex exhibited low toxicity and the Zn(II)-complex is more cytotoxic than the ligand, with the corresponding IC value of 30.01 and 47.06 μM. Both compounds had a pro-apoptotic effect without the release of reactive oxygen species (ROS) and they can interact with DNA via minor grooves driven by van der Waals forces.
Topics: Humans; Thiosemicarbazones; Ligands; Human T-lymphotropic virus 1; Chalcones; Molecular Docking Simulation; Chalcone; Human T-lymphotropic virus 2; Zinc; Antineoplastic Agents
PubMed: 37148641
DOI: 10.1016/j.jinorgbio.2023.112239 -
Medical Oncology (Northwood, London,... Oct 2023Human T-cell lymphotropic virus type 1 (HTLV-1) is the first identified human retrovirus responsible for two significant diseases: HTLV-1-associated myelopathy/tropical...
Human T-cell lymphotropic virus type 1 (HTLV-1) is the first identified human retrovirus responsible for two significant diseases: HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) and adult T-cell leukemia/lymphoma (ATLL). Although the majority of infected individuals remain asymptomatic carriers, a small percentage may develop ATLL or HAM/TSP. In tumorigenesis, a crucial process is angiogenesis, which involves the formation of new blood vessels. However, the precise mechanism of HTLV-1 associated angiogenesis remains unclear. This study aims to investigate the gene regulation involved in the angiogenesis signaling pathway associated with HTLV-1 infection. The research enrolled 20 male participants, including asymptomatic carriers and healthy individuals. Blood samples were collected and screened using ELISA for HTLV-1 confirmation, and PCR was performed for both Tax and HBZ for validation. RNA extraction and cDNA synthesis were carried out, followed by RT-qPCR analysis targeting cellular genes involved in angiogenesis. Our findings indicate that gene expression related to angiogenesis was elevated in HTLV-1 ACs patients. However, the differences in gene expression of the analyzed genes, including HSP27, Paxillin, PDK1, PTEN, RAF1, SOS1, and VEGFR2 between ACs and healthy individuals were not statistically significant. This suggests that although angiogenesis-related genes may show increased expression in HTLV-1 infection, they might not be robust indicators of ATLL progression in asymptomatic carriers. The results of our study demonstrate that angiogenesis gene expression is altered in ACs of HTLV-1, indicating potential involvement of angiogenesis in the early stages before ATLL development. While we observed elevated angiogenesis gene expression in ACs, the lack of statistical significance between ACs and healthy individuals suggests that these gene markers may not be sufficient on their own to predict the development of ATLL in asymptomatic carriers.
Topics: Adult; Humans; Male; Human T-lymphotropic virus 1; Leukemia-Lymphoma, Adult T-Cell; Signal Transduction; Carcinogenesis; Cell Transformation, Neoplastic
PubMed: 37792095
DOI: 10.1007/s12032-023-02177-5 -
Viruses Sep 2023The main mode of mother-to-child transmission of the human T-cell leukemia virus (HTLV)-1 is through breastfeeding. Although the most reliable nutritional regimen to... (Review)
Review
The main mode of mother-to-child transmission of the human T-cell leukemia virus (HTLV)-1 is through breastfeeding. Although the most reliable nutritional regimen to prevent HTLV-1 transmission is exclusive formula feeding, a recent meta-analysis revealed that short-term breastfeeding within 90 days does not increase the risk of infection. The protocol of the Japanese Health, Labor, and Welfare Science Research Group primarily recommended exclusive formula feeding for mothers who are positive for HTLV-1. However, there has been no quantitative research on the difficulties experienced by HTLV-1-positive mothers in carrying out these nutritional regimens, including the psychological burden. Therefore, this review was performed to clarify the burdens and difficulties encountered by mothers who are positive for HTLV-1; to this end, we analyzed the data registrants on the HTLV-1 career registration website "Carri-net" website. The data strongly suggest that it is not sufficient to simply recommend exclusive formula feeding or short-term breastfeeding as a means of preventing mother-to-child transmission; it is important for health care providers to understand that these nutritional regimens represent a major burden for pregnant women who are positive for HTLV-1 and to provide close support to ensure these women's health.
Topics: Humans; Female; Pregnancy; Infant; Human T-lymphotropic virus 1; Mothers; Infectious Disease Transmission, Vertical; Japan; Leukemia, T-Cell
PubMed: 37896779
DOI: 10.3390/v15102002 -
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 -
Molecular Biology Reports Sep 2023In HTLV-1-associated malignant disease, adult T-cell leukaemia/lymphoma (ATLL), the interaction of virus and host was evaluated at the chemokines gene expression level....
BACKGROUND
In HTLV-1-associated malignant disease, adult T-cell leukaemia/lymphoma (ATLL), the interaction of virus and host was evaluated at the chemokines gene expression level. Also, IL-1β and Caspase-1 expressions were evaluated to investigate the importance of pyroptosis in disease development and progression.
METHODS AND RESULTS
The expression of host CCR6 and CXCR-3 and the HTLV-1 proviral load (PVL), Tax, and HBZ were assessed in 17 HTLV-1 asymptomatic carriers (ACs) and 12 ATLL patients using the reverse transcription-quantitative polymerase chain reaction (RT-qPCR), TaqMan method. Moreover, RT-qPCR, SYBR Green assay were performed to measure Caspase-1 and IL-1β expression. HTLV-1-Tax did not express in 91.5% of the ATLLs, while HBZ was expressed in all ATLLs. The expression of CXCR3 dramatically decreased in ATLLs compared to ACs (p = 0.001). The expression of CCR6 was lower in ATLLs than ACs (p = 0.04). The mean of PVL in ATLL patients was statistically higher than ACs (p = 0.001). Furthermore, the expression of the IL-1β between ATLLs and ACs was not statistically significant (p = 0.4). In contrast, there was a meaningful difference between Caspase-1 in ATLLs and ACs (p = 0.02).
CONCLUSIONS
The present study indicated that in the first stage of ATLL malignancy toward acute lymphomatous, CXCR3 and its progression phase may target the pyroptosis process. Mainly, HBZ expression could be a novel therapeutic target.
Topics: Adult; Humans; Leukemia-Lymphoma, Adult T-Cell; Human T-lymphotropic virus 1; Biological Assay; Caspase 1; Proviruses; Gene Expression
PubMed: 37480512
DOI: 10.1007/s11033-023-08626-8 -
Tropical Animal Health and Production Sep 2023Bovine leukemia virus (BLV) causes enzootic bovine leukosis, a persistent infection and the most important neoplastic disease in cattle. It is spread primarily by...
Bovine leukemia virus (BLV) causes enzootic bovine leukosis, a persistent infection and the most important neoplastic disease in cattle. It is spread primarily by transferring infected lymphocytes through blood from carriers to healthy animals. The present study is aimed at determining the seropositivity of BLV in breeding bulls from Costa Rica and at detecting for the first time in the country BLV DNA in bull semen. Between May 2011 and August 2018, 379 blood and 133 semen samples were collected from bulls distributed in 118 farms. The serum was analyzed by an enzymatic immunoassay and the semen by polymerase chain reaction and sequencing. BLV seropositivity was 43.5% (165/379), while 64.4% (76/118) of the farms had positive reactors. Holstein (75.7%) and Jersey (73.0%) breeds showed the highest seropositivity. In addition, Bos taurus bulls (68.1%), older than seven years (50.0%), and those belonging to dairy farms (75.5%) had higher seropositivity compared to Bos indicus (17.7%), younger than seven years (42.2%), and those from beef farms (15.5%), respectively. Moreover, Bos taurus bulls had a higher risk of being seropositive than Bos indicus (OR = 3.4; 95% CI: 1.7-6.8). BLV DNA was found in one semen sample (2.5%; 1/40) from a seropositive bull. The importance of serum and molecular BLV screening in semen samples and the potential role of some risk factors associated with the disease, such as the bull's age, genotype, and type of livestock productive system, is argued in the present report.
Topics: Cattle; Animals; Male; Semen; Enzootic Bovine Leukosis; Leukemia Virus, Bovine; Costa Rica; Seroepidemiologic Studies; Cattle Diseases
PubMed: 37777681
DOI: 10.1007/s11250-023-03763-5