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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 -
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 -
Scientific Reports Oct 2023Enzootic bovine leukosis virus (BLV) and bovine herpesvirus 1 (BHV-1) are very important infectious agents for the livestock industry worldwide. The present study aimed...
Enzootic bovine leukosis virus (BLV) and bovine herpesvirus 1 (BHV-1) are very important infectious agents for the livestock industry worldwide. The present study aimed to explore the association between natural exposure to BLV and BHV-1 with sperm quality analyzed by Computer-Assisted Semen Analysis (CASA) systems. Ten sexually mature Brahman bulls, with sanitary status BLV/BHV-1 (n = 2), BLV/BHV-1 (n = 6) and BLV/BHV-1 (n = 2) were evaluated twice, 30 days apart. Results showed that sanitary status of each bull was not associated with semen quality. It was found that the quality of the semen from the second collection was better due to the interruption of sexual rest. The evidence thus revealed that a bull infected with BLV generated good-quality contaminated semen and, therefore, that it is essential to detect contaminated seminal samples to prevent the spread of BLV. A multivariate analysis showed the presence of four sperm subpopulations in Brahman bulls that differ significantly in their kinematic patterns and with respect to sanitary status (P < 0.05), indicating that infection-free and seronegative bulls present the best kinematic parameters, which improved discrimination of sperm quality according to sanitary status. Overall, the analyses indicate that the seropositive-infected bulls with BLV and BHV-1 should be excluded from beef cattle farms.
Topics: Male; Animals; Cattle; Herpesvirus 1, Bovine; Semen Analysis; Semen; Leukemia Virus, Bovine; Cattle Diseases
PubMed: 37907654
DOI: 10.1038/s41598-023-45981-9 -
Journal of Veterinary Research Mar 2024Bovine leukaemia virus (BLV) is a Deltaretrovirus responsible for enzootic bovine leukosis, the most common neoplastic disease of cattle. It deregulates the immune...
INTRODUCTION
Bovine leukaemia virus (BLV) is a Deltaretrovirus responsible for enzootic bovine leukosis, the most common neoplastic disease of cattle. It deregulates the immune system, favouring secondary infections and changes in the blood and lymphatic tissues. Blood homeostasis depends on functional haematopoietic stem cells (HSCs). Bone marrow is populated by these cells, which express CD34 and CD35 surface antigens and produce and release cytokines involved in the maintenance of haematopoiesis. The aim of the study was determination of the profile of cytokine production by CD34 stem cells of cattle naturally infected with BLV.
MATERIAL AND METHODS
The HSCs were generated from the blood and lymphoid organs of cows infected with BLV and healthy control cows with immunomagnetic separation and anti-CD34 monoclonal antibodies. Isolated CD34 cells were cultivated for two weeks with interleukin (IL)-4 and granulocyte-macrophage colony-stimulating factor. The levels of IL-6, IL-10, IL-12p40, IL-12p70, interferon gamma (IFN-γ) and tumour necrosis factor alpha (TNF-α) were determined in culture fluid by flow cytometry.
RESULTS
The expression of IL-6, IL-12p70 and TNF-α in blood HSCs was higher in BLV cows than in the control animals. In bone marrow HSCs of infected cows, IL-12, TNF-α and IFN-γ were more concentrated, but in these cows' spleen HSCs only expression of IL-10 was elevated. In HSCs isolated from the lymph nodes of leukaemic cows, only TNF-α secretion was lower than in control cows, the other cytokines being more potently secreted.
CONCLUSION
Infection with BLV caused statistically significant differences in cytokine expression by HSC CD34 cells.
PubMed: 38525233
DOI: 10.2478/jvetres-2024-0012 -
JCI Insight Jan 2024Human T cell leukemia virus type 1 (HTLV-1) is a retrovirus with preferential CD4+ T cell tropism that causes a range of conditions spanning from asymptomatic infection...
Human T cell leukemia virus type 1 (HTLV-1) is a retrovirus with preferential CD4+ T cell tropism that causes a range of conditions spanning from asymptomatic infection to adult T cell leukemia and HTLV-1-associated myelopathy (HAM), an inflammatory disease of the CNS. The mechanisms by which HTLV-1 induces HAM are poorly understood. By directly examining the ex vivo phenotype and function of T cells from asymptomatic carriers and patients with HAM, we show that patients with HAM have a higher frequency of CD4+CD8+ double-positive (DP) T cells, which are infected with HTLV-1 at higher rates than CD4+ T cells. Displaying both helper and cytotoxic phenotypes, these DP T cells are highly proinflammatory and contain high frequencies of HTLV-1-specific cells. Mechanistically, we demonstrate that DP T cells arise by direct HTLV-1 infection of CD4+ and CD8+ T cells. High levels of CD49d and CXCR3 expression suggest that DP T cells possess the ability to migrate to the CNS, and when cocultured with astrocytes, DP T cells induce proinflammatory astrocytes that express high levels of CXCL10, IFN-γ, and IL-6. These results demonstrate the potential of DP T cells to directly contribute to CNS pathology.
Topics: Humans; Astrocytes; Bone Marrow Diseases; CD4-Positive T-Lymphocytes; CD8-Positive T-Lymphocytes; Human T-lymphotropic virus 1; Paraparesis, Tropical Spastic
PubMed: 38193535
DOI: 10.1172/jci.insight.173738 -
Internal Medicine (Tokyo, Japan) Nov 2023Objective A T-SPOT.TB can yield indeterminate results under two test observation conditions: a high response to the nil in negative control wells (high nil-control) or a...
Objective A T-SPOT.TB can yield indeterminate results under two test observation conditions: a high response to the nil in negative control wells (high nil-control) or a low response to the mitogen in positive control wells (low mitogen-control). The most strongly influential factors for these indeterminate results, however, have yet to be identified. Methods From June 1, 2015, to June 30, 2021, we conducted a 1:1 matched case-control, retrospective study. Patients Patients who underwent a T-SPOT.TB test at Chiba University Hospital. Results The study included 5,956 participants. Indeterminate results were found in 63 participants (1.1%), including high nil-control in 37 and low mitogen-control in 26. Human T-cell leukemia virus type 1 (HTLV-1) positivity was the only influencing factor associated with high nil-control (adjusted odds ratio=98.5, 95% confidence interval: 6.59-1,480). Conclusion Regarding the indeterminate results, all HTLV-1 positive participants had a high nil response and no low mitogen response. It was suspected that abnormally produced interferon γ caused a nonspecific reaction to the negative control well, resulting in a high nil response. Low mitogen-control, conversely, did not appear to have any statistically significant influential factors.
Topics: Humans; Case-Control Studies; Retrospective Studies; Mitogens; Interferon-gamma; Human T-lymphotropic virus 1; Tuberculin Test; Interferon-gamma Release Tests
PubMed: 37005270
DOI: 10.2169/internalmedicine.1006-22 -
Scientific Reports Sep 2023Human T-lymphotropic virus (HTLV) infection has a worldwide distribution and currently, more than 2.5 million individuals have been infected in Brazil. The study aimed...
Human T-lymphotropic virus (HTLV) infection has a worldwide distribution and currently, more than 2.5 million individuals have been infected in Brazil. The study aimed to investigate HTLV infection prevalence among blood donors in Mato Grosso do Sul, characterizing seroepidemiological profiles of HTLV-1/2 positive individuals and evaluating the blood bank's HTLV screening system. A cross-sectional survey was conducted among blood donors from Mato Grosso do Sul state (MS)-Central Brazil, between January to December 2021. The information was obtained from databases, samples from the collection of HEMOSUL, and active searching, with the completion of laboratory analyses. 35,278 blood donors were screened for anti-HTLV-1/2 by chemiluminescence immunoassay (CMIA). Among them, 78 were initially reactive for anti-HTLV-1/2 (2.21/1000). Out of 78, 67 returned to the blood center to collect a second sample for retesting with a second screening with CMIA. After confirmation, 8 samples were indeterminate, and 8 were confirmed as positive for HTLV antibodies. New tests were performed for the 8 positive samples, and 6 were confirmed as HTLV-1 infection (0.17/1,000), one as negative, and one as indeterminate. The present study describes the low prevalence of HTLV infection in blood donors from MS and contributes to the definition of the regional infection profile. The prevalence found in this study (0.017%-0.17/1000) shows to be a much lower value than the rates reported in other states in Brazil. We highlight the need for confirmatory testing for those seropositive donors in screening assays and the need for adequate counseling and patient management for those confirmed HTLV individuals.
Topics: Humans; Brazil; Blood Banks; Blood Donors; Cross-Sectional Studies; Deltaretrovirus; Deltaretrovirus Infections; Human T-lymphotropic virus 1
PubMed: 37667056
DOI: 10.1038/s41598-023-41875-y -
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 -
The Journal of Veterinary Medical... Dec 2023A 23-month-old Holstein-Friesian heifer presented with inactivity and diarrhea. On physical examination, no enlargement of superficial lymph nodes was observed....
A 23-month-old Holstein-Friesian heifer presented with inactivity and diarrhea. On physical examination, no enlargement of superficial lymph nodes was observed. Hematological examination revealed lymphocytosis. The bovine leukemia virus (BLV) proviral load was 2,122 copies/10 ng DNA, and BLV was classified as Group C based on whole genome phylogenetic analysis. Monoclonal proliferation of B-cells and monoclonal integration of the BLV provirus in the bovine genome were detected by a clonality test of B-cells and inverse PCR, respectively. Although lymph nodes were not swollen at necropsy, histopathological examination revealed neoplastic lymphocyte proliferation in lymph nodes, which were immune positive for CD5 and CD20, and negative for CD3. The heifer was diagnosed with EBL caused by BLV classified as Group C.
Topics: Animals; Female; Cattle; Enzootic Bovine Leukosis; Leukemia Virus, Bovine; Phylogeny; Proviruses; B-Lymphocytes; Cattle Diseases
PubMed: 37914277
DOI: 10.1292/jvms.23-0354 -
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