Kinetic Study of BLV Infectivity in BLV Susceptible and Resistant Cattle in Japan from 2017 to 2019

Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leukosis. Polymorphism in bovine lymphocyte antigen (BoLA)-DRB3 alleles is related to susceptibility to BLV proviral load (PVL), which is a useful index for estimating disease progression and transmission risk. However, whether differential BoLA-DRB3 affects BLV infectivity remains unknown. In a three-year follow-up investigation using a luminescence syncytium induction assay for evaluating BLV infectivity, we visualized and evaluated the kinetics of BLV infectivity in cattle with susceptible, resistant and neutral BoLA-DRB3 alleles which were selected from 179 cattle. Susceptible cattle showed stronger BLV infectivity than both resistant and neutral cattle. The order of intensity of BLV infectivity was as follows: susceptible cattle > neutral cattle > resistant cattle. BLV infectivity showed strong positive correlation with PVL at each testing point. BLV-infected susceptible cattle were found to be at higher risk of horizontal transmission, as they had strong infectivity and high PVL, whereas BLV-infected resistant cattle were low risk of BLV transmission owing to weak BLV infection and low PVL. Thus, this is the first study to demonstrate that the BoLA-DRB3 polymorphism is associated with BLV infection.

Download Full-text

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

Pathogens ◽

10.3390/pathogens9121058 ◽

2020 ◽

Vol 9 (12) ◽

pp. 1058

Author(s):

Paul C. Bartlett ◽

Vickie J. Ruggiero ◽

Holden C. Hutchinson ◽

Casey J. Droscha ◽

Bo Norby ◽

...

Keyword(s):

Bovine Leukemia Virus ◽

Leukemia Virus ◽

Research Priorities ◽

Economic Losses ◽

Antibody Testing ◽

Enzootic Bovine Leukosis ◽

Cellular And Humoral Immunity ◽

Bovine Leukosis ◽

And Control

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.

Download Full-text

Tracing Viral Transmission and Evolution of Bovine Leukemia Virus through Long Read Oxford Nanopore Sequencing of the Proviral Genome

Pathogens ◽

10.3390/pathogens10091191 ◽

2021 ◽

Vol 10 (9) ◽

pp. 1191

Author(s):

Laura A. Pavliscak ◽

Jayaveeramuthu Nirmala ◽

Vikash K. Singh ◽

Kelly R. B. Sporer ◽

Tasia M. Taxis ◽

...

Keyword(s):

Bovine Leukemia Virus ◽

Leukemia Virus ◽

Horizontal Transmission ◽

Dairy Herd ◽

The United States ◽

Contact Tracing ◽

Nanopore Sequencing ◽

Sequence Identity ◽

Oxford Nanopore ◽

Bovine Leukosis

Bovine leukemia virus (BLV) causes Enzootic Bovine Leukosis (EBL), a persistent life-long disease resulting in immune dysfunction and shortened lifespan in infected cattle, severely impacting the profitability of the US dairy industry. Our group has found that 94% of dairy farms in the United States are infected with BLV with an average in-herd prevalence of 46%. This is partly due to the lack of clinical presentation during the early stages of primary infection and the elusive nature of BLV transmission. This study sought to validate a near-complete genomic sequencing approach for reliability and accuracy before determining its efficacy in characterizing the sequence identity of BLV proviral genomes collected from a pilot study made up of 14 animals from one commercial dairy herd. These BLV-infected animals were comprised of seven adult dam/daughter pairs that tested positive by ELISA and qPCR. The results demonstrate sequence identity or divergence of the BLV genome from the same samples tested in two independent laboratories, suggesting both vertical and horizontal transmission in this dairy herd. This study supports the use of Oxford Nanopore sequencing for the identification of viral SNPs that can be used for retrospective genetic contact tracing of BLV transmission.

Download Full-text

Increased T-cell responses that control bovine leukemia virus proviral load in beef cattle under dietary vitamin A restriction for marbling

Veterinary Immunology and Immunopathology ◽

10.1016/j.vetimm.2021.110301 ◽

2021 ◽

pp. 110301

Author(s):

Sonoko Miyauchi ◽

Yuzuru Katagiri ◽

Chihiro Ochiai ◽

Toh-ichi Hirata ◽

Keiichi Matsuda ◽

...

Keyword(s):

T Cell ◽

Vitamin A ◽

Beef Cattle ◽

Bovine Leukemia Virus ◽

Proviral Load ◽

Leukemia Virus ◽

T Cell Responses ◽

Dietary Vitamin ◽

Cell Responses

Download Full-text

Distribution of bovine leukemia virus proviral DNA sequences in tissues of animals with enzootic bovine leukosis

Leukemia Research ◽

10.1016/0145-2126(78)90004-8 ◽

1978 ◽

Vol 2 (1) ◽

pp. 23-32 ◽

Cited By ~ 26

Author(s):

Richard Kettmann ◽

Arsène Burny ◽

Yvette Cleuter ◽

Jacques Ghysdael ◽

Marc Mammerickx

Keyword(s):

Dna Sequences ◽

Bovine Leukemia Virus ◽

Leukemia Virus ◽

Enzootic Bovine Leukosis ◽

Proviral Dna ◽

Bovine Leukosis

Download Full-text

Enzootic Bovine Leukosis and Bovine Leukemia Virus

Gene Expression in Normal and Transformed Cells ◽

10.1007/978-1-4684-4541-1_11 ◽

1983 ◽

pp. 231-245

Author(s):

G. Marbaix ◽

R. Kettmann ◽

J. Deschamps ◽

D. Couez ◽

M. Mammerickx ◽

...

Keyword(s):

Bovine Leukemia Virus ◽

Leukemia Virus ◽

Enzootic Bovine Leukosis ◽

Bovine Leukosis

Download Full-text

Association between bovine leukemia virus proviral load and severity of clinical mastitis

Journal of Veterinary Medical Science ◽

10.1292/jvms.19-0285 ◽

2019 ◽

Vol 81 (10) ◽

pp. 1431-1437 ◽

Cited By ~ 2

Author(s):

Aiko WATANABE ◽

Hironobu MURAKAMI ◽

Seiichi KAKINUMA ◽

Koki MURAO ◽

Kaori OHMAE ◽

...

Keyword(s):

Bovine Leukemia Virus ◽

Proviral Load ◽

Leukemia Virus ◽

Clinical Mastitis

Download Full-text

PRMT5 Is Required for Bovine Leukemia Virus Infection In Vivo and Regulates BLV Gene Expression, Syncytium Formation, and Glycosylation In Vitro

Viruses ◽

10.3390/v12060650 ◽

2020 ◽

Vol 12 (6) ◽

pp. 650 ◽

Cited By ~ 1

Author(s):

Wlaa Assi ◽

Tomoya Hirose ◽

Satoshi Wada ◽

Ryosuke Matsuura ◽

Shin-nosuke Takeshima ◽

...

Keyword(s):

Gene Expression ◽

Small Molecule ◽

Bovine Leukemia Virus ◽

Proviral Load ◽

Leukemia Virus ◽

Syncytium Formation ◽

High Proviral Load

Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leukosis, which is the most common neoplastic disease of cattle and is closely related to human T-cell leukemia viruses. We investigated the role of a new host protein, PRMT5, in BLV infection. We found that PRMT5 is overexpressed only in BLV-infected cattle with a high proviral load, but not in those with a low proviral load. Furthermore, this upregulation continued to the lymphoma stage. PRMT5 expression was upregulated in response to experimental BLV infection; moreover, PRMT5 upregulation began in an early stage of BLV infection rather than after a long period of proviral latency. Second, siRNA-mediated PRMT5 knockdown enhanced BLV gene expression at the transcript and protein levels. Additionally, a selective small-molecule inhibitor of PRMT5 (CMP5) enhanced BLV gene expression. Interestingly, CMP5 treatment, but not siRNA knockdown, altered the gp51 glycosylation pattern and increased the molecular weight of gp51, thereby decreasing BLV-induced syncytium formation. This was supported by the observation that CMP5 treatment enhanced the formation of the complex type of N-glycan more than the high mannose type. In conclusion, PRMT5 overexpression is related to the development of BLV infection with a high proviral load and lymphoma stage and PRMT5 inhibition enhances BLV gene expression. This is the first study to investigate the role of PRMT5 in BLV infection in vivo and in vitro and to reveal a novel function for a small-molecule compound in BLV-gp51 glycosylation processing.

Download Full-text