scholarly journals BoLA-DRB3 Polymorphism is Associated with Differential Susceptibility to Bovine Leukemia Virus-Induced Lymphoma and Proviral Load

Viruses ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 352 ◽  
Author(s):  
Chieh-Wen Lo ◽  
Liushiqi Borjigin ◽  
Susumu Saito ◽  
Koya Fukunaga ◽  
Etsuko Saitou ◽  
...  
Keyword(s):  
Bovine Leukemia Virus ◽  
Proviral Load ◽  
Disease Susceptibility ◽  
Leukemia Virus ◽  
Differential Susceptibility ◽  
Leukocyte Antigen ◽  
Polymorphic Gene ◽  
Host Genetic ◽  
The Relationship ◽  
Enzootic Bovine Leucosis

Bovine leukemia virus (BLV) is the causative agent of enzootic bovine leucosis. However, less than 5% of BLV-infected cattle will develop lymphoma, suggesting that, in addition to viral infection, host genetic polymorphisms might play a role in disease susceptibility. Bovine leukocyte antigen (BoLA)-DRB3 is a highly polymorphic gene associated with BLV proviral load (PVL) susceptibility. Due to the fact that PVL is positively associated with disease progression, it is believed that controlling PVL can prevent lymphoma development. Thus, many studies have focused on the relationship between PVL and BoLA-DRB3. Despite this, there is little information regarding the relationship between lymphoma and BoLA-DRB3. Furthermore, whether or not PVL-associated BoLA-DRB3 is linked to lymphoma-associated BoLA-DRB3 has not been clarified. Here, we investigated whether or not lymphoma-associated BoLA-DRB3 is correlated with PVL-associated BoLA-DRB3. We demonstrate that two BoLA-DRB3 alleles were specifically associated with lymphoma resistance (*010:01 and *011:01), but no lymphoma-specific susceptibility alleles were found; furthermore, two other alleles, *002:01 and *012:01, were associated with PVL resistance and susceptibility, respectively. In contrast, lymphoma and PVL shared two resistance-associated (DRB3*014:01:01 and *009:02) BoLA-DRB3 alleles. Interestingly, we found that PVL associated alleles, but not lymphoma associated alleles, are related with the anti-BLV gp51 antibody production level in cows. Overall, our study is the first to demonstrate that the BoLA-DRB3 polymorphism confers differential susceptibility to BLV-induced lymphoma and PVL.

Identification of bovine leukocyte antigen class II haplotypes associated with variations in bovine leukemia virus proviral load in Japanese Black cattle

2012 ◽  
Vol 81 (2) ◽  
pp. 72-82 ◽  
Author(s):  
T. Miyasaka ◽  
S.-n. Takeshima ◽  
M. Jimba ◽  
Y. Matsumoto ◽  
N. Kobayashi ◽  
...  
Keyword(s):  
Bovine Leukemia Virus ◽  
Proviral Load ◽  
Leukemia Virus ◽  
Class Ii ◽  
Japanese Black Cattle ◽  
Leukocyte Antigen

scholarly journals Phenotypic Selection of Dairy Cattle Infected with Bovine Leukemia Virus Demonstrates Immunogenetic Resilience through NGS-Based Genotyping of BoLA MHC Class II Genes

Pathogens ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 104
Author(s):  
Chaelynne E. Lohr ◽  
Kelly R. B. Sporer ◽  
Kelsey A. Brigham ◽  
Laura A. Pavliscak ◽  
Matelyn M. Mason ◽  
...  
Keyword(s):  
Dairy Cattle ◽  
Mhc Class Ii ◽  
Bovine Leukemia Virus ◽  
Proviral Load ◽  
Leukemia Virus ◽  
Phenotypic Selection ◽  
Field Trials ◽  
Susceptible Population ◽  
Leukocyte Antigen ◽  
Study Population

Characterization of the bovine leukocyte antigen (BoLA) DRB3 gene has shown that specific alleles associate with susceptibility or resilience to the progression of bovine leukemia virus (BLV), measured by proviral load (PVL). Through surveillance of multi-farm BLV eradication field trials, we observed differential phenotypes within seropositive cows that persist from months to years. We sought to develop a multiplex next-generation sequencing workflow (NGS-SBT) capable of genotyping 384 samples per run to assess the relationship between BLV phenotype and two BoLA genes. We utilized longitudinal results from milk ELISA screening and subsequent blood collections on seropositive cows for PVL determination using a novel BLV proviral load multiplex qPCR assay to phenotype the cows. Repeated diagnostic observations defined two distinct phenotypes in our study population, ELISA-positive cows that do not harbor detectable levels of provirus and those who do have persistent proviral loads. In total, 565 cows from nine Midwest dairy farms were selected for NGS-SBT, with 558 cows: 168 BLV susceptible (ELISA-positive/PVL-positive) and 390 BLV resilient (ELISA-positive/PVL-negative) successfully genotyped. Three BoLA-DRB3 alleles, including one novel allele, were shown to associate with disease resilience, *009:02, *044:01, and *048:02 were found at rates of 97.5%, 86.5%, and 90.3%, respectively, within the phenotypically resilient population. Alternatively, DRB3*015:01 and *027:03, both known to associate with disease progression, were found at rates of 81.1% and 92.3%, respectively, within the susceptible population. This study helps solidify the immunogenetic relationship between BoLA-DRB3 alleles and BLV infection status of these two phenotypic groupings of US dairy cattle.

scholarly journals Association of Bovine Leukemia Virus-Induced Lymphoma with BoLA-DRB3 Polymorphisms at DNA, Amino Acid, and Binding Pocket Property Levels

Pathogens ◽  
2021 ◽  
Vol 10 (4) ◽  
pp. 437
Author(s):  
Chieh-Wen Lo ◽  
Shin-nosuke Takeshima ◽  
Kosuke Okada ◽  
Etsuko Saitou ◽  
Tatsuo Fujita ◽  
...  
Keyword(s):  
Amino Acid ◽  
Bovine Leukemia Virus ◽  
Association Studies ◽  
Leukemia Virus ◽  
B Cell Lymphoma ◽  
Structural Diversity ◽  
Binding Pocket ◽  
Japanese Black Cattle ◽  
Leukocyte Antigen ◽  
The Relationship

Bovine leukemia virus (BLV) causes enzootic bovine leucosis, a malignant B-cell lymphoma in cattle. The DNA sequence polymorphisms of bovine leukocyte antigen (BoLA)-DRB3 have exhibited a correlation with BLV-induced lymphoma in Holstein cows. However, the association may vary between different cattle breeds. Furthermore, little is known about the relationship between BLV-induced lymphoma and DRB3 at the amino acid and structural diversity levels. Here, we comprehensively analyzed the correlation between BLV-induced lymphoma and DRB3 at DNA, amino acid, and binding pocket property levels, using 106 BLV-infected asymptomatic and 227 BLV-induced lymphoma Japanese black cattle samples. DRB3*011:01 was identified as a resistance allele, whereas DRB3*005:02 and DRB3*016:01 were susceptibility alleles. Amino acid association studies showed that positions 9, 11, 13, 26, 30, 47, 57, 70, 71, 74, 78, and 86 were associated with lymphoma susceptibility. Structure and electrostatic charge modeling further indicated that binding pocket 9 of resistance DRB3 was positively charged. In contrast, alleles susceptible to lymphoma were neutrally charged. Altogether, this is the first association study of BoLA-DRB3 polymorphisms with BLV-induced lymphoma in Japanese black cattle. In addition, our results further contribute to understanding the mechanisms regarding how BoLA-DRB3 polymorphisms mediate susceptibility to BLV-induced lymphoma.

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

2019 ◽  
Vol 81 (10) ◽  
pp. 1431-1437 ◽  
Author(s):  
Aiko WATANABE ◽  
Hironobu MURAKAMI ◽  
Seiichi KAKINUMA ◽  
Koki MURAO ◽  
Kaori OHMAE ◽  
...  
Keyword(s):  
Bovine Leukemia Virus ◽  
Proviral Load ◽  
Leukemia Virus ◽  
Clinical Mastitis

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

Viruses ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 650 ◽  
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.

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