Bovine Leukemia Virus Infection Research Articles

Bovine major histocompatibility complex (BoLA) heterozygote advantage against the outcome of bovine leukemia virus infection.

Bovine leukemia virus (BLV) causes enzootic bovine leucosis. Host genetic heterozygosity at the major histocompatibility complex can enhance the ability to combat infectious diseases. However, heterozygote advantage is loci specific and depends on disease type. Bovine leukocyte antigen (BoLA)-DRB3 polymorphisms are related with BLV-infection outcome; however, whether BoLA-DRB3 heterozygotes have an advantage against BLV-induced lymphoma and proviral load (PVL) remains unclear. By analyzing 1567 BLV-infected individuals, we found that BoLA-DRB3 heterozygous status was significantly associated with lymphoma resistance irrespective of cattle breeds (p < 0.0001). Similarly, decreased PVL was observed in BoLA-DRB3 heterozygotes (p=0.0407 for Holstein cows; p=0.0889 for Japanese Black cattle). Our report provides first evidence of BoLA-DRB3 heterozygote advantage against BLV infection outcome.

ЛЕЙКОЗ КРУПНОГО РОГАТОГО СКОТА — ДИАГНОСТИКА, ОЗДОРОВЛЕНИЕ, АНТРОПОЗООНОЗНЫЙ ПОТЕНЦИАЛ (ИСТОРИЯ ВОПРОСА) (обзор)

Of tumor diseases in the global animal husbandry industry, the greatest danger is bovine leukemia. Since the last century, this neoplastic disease has remained relevant for veterinary medicine and, in addition, more and more questions arise concerning the potential threat of the Bovine leukemia virus (BLV) for humans. The problem is being discussed (G.Yu. Kosovskiy et al., 2016) which additionally stimulates both fundamental research of the pathogen and the pathology, as well as the methods for detection to improve dairy cattle breeding and veterinary safety. A number of publications are devoted to BLV prevalence, peculiarities, the prospects for improving animal health and welfare based on selection and vaccines developed in the world (S.G. Hopkins et al., 1997; M.A. Juliarena et al., 2017). In our report, we retrospectively compare the experience of BLV eradication in the USSR, Russia and abroad, additionally focusing on the possible role of this pathogen in the occurrence of cancer in humans. In veterinary practice, serological tests, i.e., immunodiffusion (ID) assay in agar gel and enzyme-linked immunosorbent assay (ELISA) are mostly used to detect the BLV infection. G.C. Buehring et al. (2019) reported the detection of BLV proviral DNA in blood leukocytes in 38 % of patients examined by PCR and DNA sequencing. IgG antibodies to BLV were detected in 32 %, IgM — in 58 %, and IgA — in 32 % of the samples tested. Accumulated data indicate metabolic changes in the BLV-positive animals, e.g., disorder in the metabolism of tryptophan, a critical essential acid, leading to the accumulation of dangerous endogenous metabolites in the body. Particularly, free tryptophan, indole and anthranilic acid increased in level 4-8-fold are deposited in the organs of the immune and hematopoietic system (lymph nodes, spleen, liver), in the mammary gland, lungs, and kidneys. It has been established that the milk of leukemic animals differs from the milk of healthy cows in terms of physicochemical, bacteriological (lysozyme), technological parameters and mineral composition. In C57 mice fed with pasteurized milk and heat-treated meat from ID-positive cows, the blood cell profile changed. Available data drive to the unambiguous conclusion that the products derived from BLV-infected cattle pose an increased risk to humans. Despite the lack of convincing evidence of the BLV pathogenicity for humans, concerns about the etiological role of this virus in the occurance of cancer in humans additionally necessitates continuing research on the control and eradication of this common oncogenic retro-virus in livestock farms.

Bovine leukemia virus INFECTION — DIAGNOSTICS, ERADICATION, AND ANTHROPOZOONOTIC POTENTIAL (BACKGROUND) (review)

Of tumor diseases in the global animal husbandry industry, the greatest danger is bovine leukemia. Since the last century, this neoplastic disease has remained relevant for veterinary medicine and, in addition, more and more questions arise concerning the potential threat of the Bovine leukemia virus (BLV) for humans. The problem is being discussed (G.Yu. Kosovskiy et al., 2016) which additionally stimulates both fundamental research of the pathogen and the pathology, as well as the methods for detection to improve dairy cattle breeding and veterinary safety. A number of publications are devoted to BLV prevalence, peculiarities, the prospects for improving animal health and welfare based on selection and vaccines developed in the world (S.G. Hopkins et al., 1997; M.A. Juliarena et al., 2017). In our report, we retrospectively compare the experience of BLV eradication in the USSR, Russia and abroad, additionally focusing on the possible role of this pathogen in the occurrence of cancer in humans. In veterinary practice, serological tests, i.e., immunodiffusion (ID) assay in agar gel and enzyme-linked immunosorbent assay (ELISA) are mostly used to detect the BLV infection. G.C. Buehring et al. (2019) reported the detection of BLV proviral DNA in blood leukocytes in 38 % of patients examined by PCR and DNA sequencing. IgG antibodies to BLV were detected in 32 %, IgM — in 58 %, and IgA — in 32 % of the samples tested. Accumulated data indicate metabolic changes in the BLV-positive animals, e.g., disorder in the metabolism of tryptophan, a critical essential acid, leading to the accumulation of dangerous endogenous metabolites in the body. Particularly, free tryptophan, indole and anthranilic acid increased in level 4-8-fold are deposited in the organs of the immune and hematopoietic system (lymph nodes, spleen, liver), in the mammary gland, lungs, and kidneys. It has been established that the milk of leukemic animals differs from the milk of healthy cows in terms of physicochemical, bacteriological (lysozyme), technological parameters and mineral composition. In C57 mice fed with pasteurized milk and heat-treated meat from ID-positive cows, the blood cell profile changed. Available data drive to the unambiguous conclusion that the products derived from BLV-infected cattle pose an increased risk to humans. Despite the lack of convincing evidence of the BLV pathogenicity for humans, concerns about the etiological role of this virus in the occurance of cancer in humans additionally necessitates continuing research on the control and eradication of this common oncogenic retro-virus in livestock farms.

Risk Assessment of Bovine Major Histocompatibility Complex Class II DRB3 Alleles for Perinatal Transmission of Bovine Leukemia Virus.

Perinatal transmission plays a critical role in the spread of bovine leukemia virus (BLV) infection in cattle herds. In the Holstein breed, we previously identified BLV resistant and susceptible bovine leukocyte antigen (BoLA)-DRB3 alleles, including BoLA-DRB3*009:02 and *014:01:01 with a low BLV proviral load (PVL), and *015:01 and *012:01 with a high PVL. Here, we evaluated the perinatal BLV transmission risk in dams with different BoLA-DRB3 alleles. BoLA-DRB3 alleles of 120 dam-calf pairs from five dairy farms in Japan were identified; their PVL was quantified using the BLV-Coordination of Common Motifs (CoCoMo)-qPCR-2 assay. Ninety-six dams were BLV-positive, and 29 gave birth to BLV-infected calves. Perinatal transmission frequency was 19% in dams with resistant alleles suppressed to a low PVL level, and 38% and 25% in dams with susceptible and neutral alleles that maintained high PVL levels, respectively. Notably, all calves with resistant alleles were BLV free, whereas 30% of calves with susceptible genes were infected. Thus, vertical transmission risk was extremely lower for dams and calves with resistant alleles compared to those with susceptible alleles. Our results can inform the development of effective BLV eradication programs under field conditions by providing necessary data to allow for optimal selection of dams for breeding.

Bovine leukemia viral DNA found on human breast tissue is genetically related to the cattle virus

Bovine leukemia virus (BLV) infection is widespread in cattle and associated with B cell lymphoma. In a previous study we demonstrated that bovine leukemia viral DNA was detected in human breast tissues and significantly associated with breast cancer. Our current study aimed to determine whether BLV DNA found in humans and cattle at the same geographical region were genetically related. DNA was extracted from the breast tissue of healthy (n = 32) or cancerous women patients (n = 27) and from the blood (n = 30) of cattle naturally infected with BLV, followed by PCR-amplification and partial nucleotide sequencing of the BLV env gene. We found that the nucleotide sequence identity between BLV env gene fragments obtained from human breast tissue and cattle blood ranged from 97.8 to 99.7% and grouped into genotype 1. Thus, our results further support the hypothesis that this virus might cause a zoonotic infection.

A target enrichment high throughput sequencing system for characterization of BLV whole genome sequence, integration sites, clonality and host SNP

Bovine leukemia virus (BLV) is an oncogenic retrovirus which induces malignant lymphoma termed enzootic bovine leukosis (EBL) after a long incubation period. Insertion sites of the BLV proviral genome as well as the associations between disease progression and polymorphisms of the virus and host genome are not fully understood. To characterize the biological coherence between virus and host, we developed a DNA-capture-seq approach, in which DNA probes were used to efficiently enrich target sequence reads from the next-generation sequencing (NGS) library. In addition, enriched reads can also be analyzed for detection of proviral integration sites and clonal expansion of infected cells since the reads include chimeric reads of the host and proviral genomes. To validate this DNA-capture-seq approach, a persistently BLV-infected fetal lamb kidney cell line (FLK-BLV), four EBL tumor samples and four non-EBL blood samples were analyzed to identify BLV integration sites. The results showed efficient enrichment of target sequence reads and oligoclonal integrations of the BLV proviral genome in the FLK-BLV cell line. Moreover, three out of four EBL tumor samples displayed multiple integration sites of the BLV proviral genome, while one sample displayed a single integration site. In this study, we found the evidence for the first time that the integrated provirus defective at the 5′ end was present in the persistent lymphocytosis cattle. The efficient and sensitive identification of BLV variability, integration sites and clonal expansion described in this study provide support for use of this innovative tool for understanding the detailed mechanisms of BLV infection during the course of disease progression.

Seroprevalence, Risk Factors and Molecular Identification of Bovine Leukemia Virus in Egyptian Cattle.

Simple SummaryBovine leukemia virus (BLV) is distributed worldwide and affects dairy cattle causing significant economic losses. This study’s objective was to assess the risk factors associated with BLV infection and identify the Egyptian BLV strain’s genetic diversity. The overall seroprevalence of BLV infection in Egyptian dairy cattle was 18.2%, and the grazing cattle in the losing house system had a higher probability of getting BLV infection. The sequencing and phylogenetic analysis for one Egyptian BLV strain was performed, and the obtained results confirmed the clustering of Egyptian BLV strain into genotype-1.Bovine leukemia virus (BLV) is distributed worldwide and affects dairy cattle causing severe economic losses. The BLV has been serologically reported in Egypt, but few studies have evaluated its associated risk factors and genetic classification. Therefore, this study assessed risk factors associated with BLV infection and identified the genetic diversity of the Egyptian strain. The study was conducted on 500 dairy cattle distributed in four Governorates located in Northern Egypt. Overall, the seroprevalence of BLV infection among Egyptian dairy cattle was 18.2%. The grazing cattle in the losing house system had higher odds for BLV seropositivity, and bad practice such as the use of a single needle or one plastic glove for more than one animal was considered a significant risk factor for BLV infection. Besides, the sequencing and phylogenetic analysis for one Egyptian BLV strain was performed, and the obtained results confirmed the clustering of Egyptian BLV strain into genotype-1. The assessment of associated risk factors for BLV infection and determination of its genetic classification are essential to implement an effective control program.

Molecular characterization of bovine foamy virus and its association with bovine leukemia virus infection in Vietnamese cattle.

The detection of bovine foamy virus (BFV) in Vietnamese cattle was performed using conventional PCR targeting pol and gag genes. Out of 243 tested samples, ten (4.1%) and eight (3.3%) samples were positive for BFV gag and pol DNA, respectively. The prevalence of bovine leukemia virus (BLV) estimated by detection of proviral DNA using nested PCR targeting env gene was 26.7% (65/243). The results of nucleotide sequence alignment and the phylogenetic analysis suggested that Vietnamese BFV strains showed high homology to isolates belonging to either European or non-European clades. There was no significant correlation between BLV and BFV. This study provides information regarding BFV infection and confirms the existence of two BFV clades among Vietnamese cattle for the first time.

Identification of bovine leukemia virus in raw milk samples in North-West of Iran.

Bovine leukemia virus (BLV) is one of the most important carcinogenic viruses genetically related to the human T-cell lymphotropic viruses (HTLV-1 and HTLV-2). The virus infects type B lymphocytes and creates lymph glands tumors. Recently, the association between the presence of this virus and breast cancer has been addressed in humans. Here, we studied the prevalence of BLV in the samples of raw milk of native Iranian and Iranian-foreign cows in traditional, semi-industrial and industrial dairy farms in rural and urban areas of Zanjan province. Raw milk samples of cows were collected manually in sterile tubes. The samples were tested by nested-PCR method. Forty samples (9.93%) out of 403 samples showed BLV contamination. In this study, nested-PCR was successfully applied to determine the level of contamination in raw milk samples from cows infected with BLV. Furthermore, a relatively high rate of BLV infection was found in dairy cows in Zanjan province, northwestern of Iran.

Diagnostic Role of Circulating Immune Complexes During Cow Leukemia

In chronic infections caused by retroviruses, antigen antibody immune complexes (AAC) appear in body fluids. In the course of the studies to clarify the structure of the AAC we proved that immune complexes in cattle leukemia could contain the virus's viral DNA. The role of circulating immune complexes in the pathogenesis of the bovine leukemia virus (BLV) infection is not sufficiently studied. AAC containing the viral DNA may be formed during the death of infected B-lymphocytes by linking non-invasive viral DNA to surface IgMs with high DNA affinity. Determining the appearance of AAC with the viral DNA in biological fluids depending on the stages of the infectious process is an important criterion in antileukemia measures. The article describes the results of research to determine circulating immune complexes containing the provirus DNA in the milk of cows infected with BLV as compared with hematological changes at different stages of the infection process. It is reported that the viral DNA in the AAC of the milk of cows infected with BLV is detected much earlier than hematological changes that allow to consider them leukemia patients. Of the 12 cows studied, by the end of the experiment, six cows had AAC containing the viral DNA in their milk samples. And only one cow with the detection of the viral DNA in the AAC of milk showed parallel hematological changes typical for leukemia. The use of milk samples for molecular genetic analysis to identify BLV in AAC is quite a promising area for assessing the epizootic situation on farms and is very informative in determining the animal status.

Current Developments in the Epidemiology and Control of Enzootic Bovine Leukosis as Caused by Bovine Leukemia Virus.

Enzootic Bovine Leukosis (EBL) caused by the bovine leukemia virus (BLV) has been eradicated in over 20 countries. In contrast, the U.S. and many other nations are experiencing increasing prevalence in the absence of efforts to control transmission. Recent studies have shown that BLV infection in dairy cattle has a greater impact beyond the long-recognized lymphoma development that occurs in <5% of infected cattle. Like other retroviruses, BLV appears to cause multiple immune system disruptions, affecting both cellular and humoral immunity, which are likely responsible for increasingly documented associations with decreased dairy production and decreased productive lifespan. Realization of these economic losses has increased interest in controlling BLV using technology that was unavailable decades ago, when many nations eradicated BLV via traditional antibody testing and slaughter methods. This traditional control is not economically feasible for many nations where the average herd antibody prevalence is rapidly approaching 50%. The ELISA screening of cattle with follow-up testing via qPCR for proviral load helps prioritize the most infectious cattle for segregation or culling. The efficacy of this approach has been demonstrated in at least four herds. Breeding cattle for resistance to BLV disease progression also appears to hold promise, and several laboratories are working on BLV vaccines. There are many research priorities for a wide variety of disciplines, especially including the need to investigate the reports linking BLV and human breast cancer.

Study of episootic situation and dynamics of episootic and infectious processes of bovine leukemia infection

One of the problems in dairy cattle breeding has become bovine leukemia since the middle of the 20th century in the Republic of Belarus. Initially, isolated cases of the disease were recorded according to the data of clinical signs and pathological changes in the case of death of animals and the results of veterinary sanitary examination at the section of meat processing plants. After the establishment of the infectious etiology of the disease and the introduction of the immune diffusion reaction into veterinary laboratory practice, the massive nature of its spread was established with corresponding economic losses for the livestock industry. Under the prevailing conditions, it was necessary to reliably study the indicators of the epizootic situation and the trends of the epizootic process affecting the spread of infection with the bovine leukemia virus in order to take effective measures to eliminate it. The authors considered the methodological approaches to the study of the epizootic situation and the dynamics of the epizootic process of bovine leukemia virus infection in the Republic of Belarus formed the basis of the developed monitoring system. It included 132 epizootic significant indicators, divided into 8 groups, reflecting the epizootic situation of bovine leukemia virus infection, taking into account age, sex, production, territorial and other characteristics of infectious and epizootic processes of the disease in the conditions of the Republic of Belarus, established the procedure for collecting and transmitting epizootic information for making management decisions. This made it possible to control the epizootic situation and predict its development, to determine the features and patterns of the epizootic process, to evaluate the results of diagnostic studies, the effectiveness of anti-leukemic measures and their socio-economic significance. The use of epizootic, clinical, pathomorphological, laboratory methods of research with subsequent statistical processing of the data obtained and their analysis in the monitoring system of infection of the cattle leukemia virus in the Republic of Belarus made it possible to control the epizootic situation, predict its development, determine the features and patterns of the epizootic process, evaluate the results of diagnostic research, the effectiveness of anti-leukemic measures and their socio-economic significance.

Prevalence of bovine leukemia in 1983–2019 in China: A systematic review and meta-analysis

Bovine leukemia is a chronic, progressive, contagious tumor disease characterized by malignant lymphoid cell hyperplasia and systemic lymphadenopathy, and is caused by bovine leukemia virus (BLV). The disease affects almost all countries and regions where livestock are raised, and may even be a potential zoonotic disease. Monitoring and early prevention of bovine leukemia is very important. Therefore, we conducted this meta-analysis, the first of its type in the country, to estimate the prevalence of bovine leukemia in 1983–2019 in China. We included a total of 35 publications reported in 1983–2019 from the PubMed, ScienceDirect, Chinese Web of Knowledge (CNKI), VIP Chinese, and Wan Fang databases. In those articles, a total of 34,954 cattle had been tested, of which 4701 were positive for BLV infection. The estimated pooled BLV prevalence was 10.0% (4701/34,954). Subgroup analysis showed that there were significant differences for sampling years, detection methods, and age. BLV prevalence was highest in the following subgroups: sampled before 1985 (38.5%, 437/1134), age 3–5 years (22.5%, 231/1044), and detected by PCR (17.9%, 1228/5100). Regarding geographic factors, there were significant differences in the latitude and elevation subgroups. BLV prevalence was lowest in the subgroups of 20–30° latitude (3.3%, 255/5069) 200–1000 m altitude (2.2%, 560/11,990). We also analyzed other subgroups such as region, variety, breeding method, precipitation, humidity, and temperature, however, the differences were not significant. Our research indicated that the BLV was still prevalent in some of areas in China. We recommend strengthening the testing of cattle aged >1 year and using flexible testing methods such as PCR to control the prevalence of bovine leukemia and to prevent persistent infection.

Expression-based analysis of genes related to single nucleotide polymorphism hits associated with bovine leukemia virus proviral load in Argentinean dairy cattle

In dairy cattle infected with bovine leukemia virus (BLV), the proviral load (PVL) level is directly related to the viral transmission from infected animals to their healthy herdmates. Two contrasting phenotypic groups can be identified when assessing PVL in peripheral blood of infected cows. A large number of reports point to bovine genetic variants (single nucleotide polymorphisms) as one of the key determinants underlying PVL level. However, biological mechanisms driving BLV PVL profiles and infection progression in cattle have not yet been elucidated. In this study, we evaluated whether a set of candidate genes affecting BLV PVL level according to whole genome association studies are differentially expressed in peripheral blood mononuclear cells derived from phenotypically contrasting groups of BLV-infected cows. During a 10-mo-long sampling scheme, 129 Holstein cows were phenotyped measuring anti-BLV antibody levels, PVL quantification, and white blood cell subpopulation counts. Finally, the expression of 8 genes (BOLA-DRB3, PRRC2A, ABT1, TNF, BAG6, BOLA-A, LY6G5B, and IER3) located within the bovine major histocompatibility complex region harboring whole genome association SNP hits was evaluated in 2 phenotypic groups: high PVL (n = 7) and low PVL (n = 8). The log2 initial fluorescence value (N0) transformed mean expression values for the ABT1 transcription factor were statistically different in high- and low-PVL groups, showing a higher expression of the ABT1 gene in low-PVL cows. The PRRC2A and IER3 genes had a significant positive (correlation coefficient = 0.61) and negative (correlation coefficient = -0.45) correlation with the lymphocyte counts, respectively. Additionally, the relationships between gene expression values and lymphocyte counts were modeled using linear regressions. Lymphocyte levels in infected cows were better explained (coefficient of determination = 0.56) when fitted a multiple linear regression model using both PRRC2A and IER3 expression values as independent variables. The present study showed evidence of differential gene expression between contrasting BLV infection phenotypes. These genes have not been previously related to BLV pathobiology. This valuable information represents a step forward in understanding the BLV biology and the immune response of naturally infected cows under a commercial milk production system. Efforts to elucidate biological mechanisms leading to BLV infection progression in cows are valuable for BLV control programs. Further studies integrating genotypic data, global transcriptome analysis, and BLV progression phenotypes are needed to better understand the BLV-host interaction.

Bovine Leukemia Virus Infection Affects Host Gene Expression Associated with DNA Mismatch Repair.

Bovine leukemia virus (BLV) causes enzootic bovine leukosis, a malignant form of B-cell lymphoma, and is closely related to human T-cell leukemia viruses. We investigated whether BLV infection affects host genes associated with DNA mismatch repair (MMR). Next-generation sequencing of blood samples from five calves experimentally infected with BLV revealed the highest expression levels of seven MMR genes (EXO1, UNG, PCNA, MSH2, MSH3, MSH6, and PMS2) at the point of peak proviral loads (PVLs). Furthermore, MMR gene expression was only upregulated in cattle with higher PVLs. In particular, the expression levels of MSH2, MSH3, and UNG positively correlated with PVL in vivo. The expression levels of all seven MMR genes in pig kidney-15 cells and the levels of PMS2 and EXO1 in HeLa cells also increased tendencies after transient transfection with a BLV infectious clone. Moreover, MMR gene expression levels were significantly higher in BLV-expressing cell lines compared with those in the respective parental cell lines. Expression levels of MSH2 and EXO1 in BLV-infected cattle with lymphoma were significantly lower and higher, respectively, compared with those in infected cattle in vivo. These results reveal that BLV infection affects MMR gene expression, offering new candidate markers for lymphoma diagnosis.

Quantitative Risk Assessment for the Introduction of Bovine Leukemia Virus-Infected Cattle Using a Cattle Movement Network Analysis.

The cattle industry is suffering economic losses caused by bovine leukemia virus (BLV) and enzootic bovine leukosis (EBL), the clinical condition associated with BLV infection. This pathogen spreads easily without detection by farmers and veterinarians due to the lack of obvious clinical signs. Cattle movement strongly contributes to the inter-farm transmission of BLV. This study quantified the farm-level risk of BLV introduction using a cattle movement analysis. A generalized linear mixed model predicting the proportion of BLV-infected cattle was constructed based on weighted in-degree centrality. Our results suggest a positive association between weighted in-degree centrality and the estimated number of introduced BLV-infected cattle. Remarkably, the introduction of approximately six cattle allowed at least one BLV-infected animal to be added to the farm in the worst-case scenario. These data suggest a high risk of BLV infection on farms with a high number of cattle being introduced. Our findings indicate the need to strengthen BLV control strategies, especially along the chain of cattle movement.

Genetic variation in Japanese Holstein cattle for EBL development

BackgroundInfection with bovine leukemia virus (BLV), the causative agent for enzootic bovine leukosis (EBL), is increasing in dairy farms of Japan. The tendency of tumor development following BLV infection in certain cow families and bull lines has previously been described. We therefore hypothesized the existence of a genetic component which differentiates cattle susceptibility to the disease.ResultsWe analyzed routinely collected large-scale data including postmortem inspection data, which were combined with pedigree information and epidemiological data of BLV infection. A total of 6,022 postmortem inspection records of Holstein cattle, raised on 226 farms served by a regional abattoir over 10 years from 2004 to 2015, were analyzed for associations between sire information and EBL development. We then identified statistically the relative susceptibility to EBL development for the progeny of specific sires and paternal grandsires (PGSs). The heritability of EBL development was calculated as 0.19. Similarly, proviral loads (PVLs) of progeny from identified sires and PGSs were analyzed, but no significant differences were found.ConclusionsThese observations suggest that because EBL development in our Holstein population is, at least in part, influenced by genetic factors independent of PVL levels, genetic improvement for lower incidence of EBL development in cattle notwithstanding BLV infection is possible.

ELEMENTS OF DNA-TECHNOLOGY FORMING QUALITY AND SAFE RAW MATERIALS

It is known that cows high milk productivity is associated with decrease in resistance to various diseases, including bovine leukosis, in resistance formation to which the BoLA-DRB3 gene plays role, whose alleles are associated with resistance (R-alleles *7, *11, *23, *28), sensitivity (S-alleles *8, *16, *22, *24) or are defined as neutral (N) in relation to the disease. Researchers also established association of BoLA-DRB3-alleles *8, *11, *23 with an increased milk yield volume, and the *22 allele - with reduced milk yield volume. The aim of research was to study associative communication of servicing bulls BoLA-DRB3 genotypes groups with their breeding value by female ancestor’s dairy productivity indicators. As a result, we studied associative communication of servicing bulls BoLA-DRB3 genotypes groups with their breeding value by female ancestor’s dairy productivity indicators with identification of reduced milk productivity with genetic resistance to bovine leukemia virus infection and bovine leukosis disease relationship, as well as observation of positive correlation between increased milk productivity and genetic predisposition to increased milk yield volumes. The obtained information will be taken into account in breeding during dairy herds reproduction with genetic resistance to bovine leukosis.

High positivity values for bovine leukemia virus in human breast cancer cases from Minas Gerais, Brazil.

Bovine leukemia virus (BLV) is a retrovirus that causes lymphoma in cattle worldwide and has also been associated with breast cancer in humans. The mechanism of BLV infection in humans and its implication as a primary cause of cancer in women are not known yet. BLV infection in humans may be caused by the consumption of milk and milk-products or meat from infected animals. Breast cancer incidence rates in Brazil are high, corresponding to 29.5% a year of cancer cases among women. In 2020, an estimated 66,280 new cases of breast cancer are expected, whereas in 2018 breast cancer has led to 17,572 deaths, the highest incidence and lethality among cancers in women in this country that year. BLV infection occurrence ranges from 60 to 95% in dairy herds. In addition, there are some regions, such as the Minas Gerais State, southeastern Brazil, where the population traditionally consume unpasteurized dairy products. Taken together, this study aimed to verify if there is a higher association between breast cancer and the presence of BLV genome in breast tissue samples within this population that consumes raw milk from animals with high rates of BLV infection. A molecular study of two BLV genes was carried out in 88 breast parenchyma samples, between tumors and controls. The amplified fragment was subjected to BLV proviral sequencing and its identity was confirmed using GenBank. BLV proviral genes were amplified from tumor breast parenchyma samples and healthy tissue control samples from women, revealing a 95.9% (47/49) and 59% (23/39) positivity, respectively. Our results show the highest correlation of BLV and human breast cancer found in the world to date within the population of Minas Gerais, Brazil.

A TLR7 agonist activates bovine Th1 response and exerts antiviral activity against bovine leukemia virus

Bovine leukemia virus (BLV) infection is a bovine chronic infection caused by BLV, a member of the genus Deltaretrovirus. In this study, we examined the immunomodulatory effects of GS-9620, a toll-like receptor (TLR) 7 agonist, in cattle (Bos taurus) and its therapeutic potential for treating BLV infection. GS-9620 induced cytokine production in peripheral blood mononuclear cells (PBMCs) as well as CD80 expression in CD11c+ cells and increased CD69 and interferon (IFN)-γ expressions in T cells. Removing CD11c+ cells from PBMCs decreased CD69 expression in T cells in the presence of GS-9620. These results suggest that TLR7 agonism promotes T-cell activation via CD11c+ cells. Analyses using PBMCs from BLV-infected cattle revealed that TLR7 expression in CD11c+ cells was upregulated during late-stage BLV infection. Furthermore, GS-9620 increased IFN-γ and TNF-α production and inhibited syncytium formation in vitro, suggesting that GS-9620 may be used to treat BLV infection.