Background
As the causative agent of enzootic bovine leukosis (EBL), bovine leukemia virus (BLV) is a retrovirus and an oncogenic member of the Deltaretrovirus genus. Most BLV-infected cattle are asymptomatic carriers of the virus, but it has been shown that although lymphocyte counts are not elevated in cattle that are asymptomatic carriers, there is an increase in CD5+IgM+B cells, and additionally this group of cattle may exhibit some degree of immune dysregulation, leading to economic losses including reduced milk production, high incidence of infectious diseases, and reproductive inefficiency. The clinical symptoms of tumors induced by BLV are various, including digestive disorders, weight loss, weakness, loss of appetite, decreased milk production and lymph node enlargement.
The BLV genome consists of 8714 nucleotides. It includes essential structural proteins, enzyme-coding genes, and a pX region flanked by two identical long terminal repeats (LTRs). Structural proteins and enzyme-coding genes, namely gag, pro, pol, and env, play indispensable roles in the virus life cycle, virus infectivity, and production of infectious virus particles. The gag gene of BLV is translated into pre-Pr45 gag and processed to produce three mature proteins. The matrix protein p15, which binds to the viral genomic RNA and interacts with the lipid bilayer of the viral membrane; the capsid protein p24, which is the main target of host immune response, is found to have a high antibody titer against this molecule in the serum of infected animals, and the nucleocapsid protein p12 binds to the packaged genomic RNA. The env gene encodes the mature extracellular protein gp51 and the transmembrane protein gp30. The pX region between env and the 3′ LTR encodes the regulatory proteins Tax and Rex, as well as the accessory proteins R3 and G4. Regulatory proteins are important for the regulation of viral transcription, the transformation of BLV-induced leukemogenesis, and the nuclear export of viral RNA to the cytoplasm. R3 and G4 accessory proteins contribute to the maintenance of high viral loads.
Figure 1. Schematic representations of the BLV genome structure (a) and viral particle (b)
(Source: Polat M, et al. 2017)
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Alternative Names
BLV gp51
BLV envelope glycoprotein 51
References
- 1. Polat M, et al. Epidemiology and genetic diversity of bovine leukemia virus. Virol J. 2017 Nov 2;14(1):209.
- 2. Juliarena M, et al. Bovine leukemia virus: current perspectives. Virus Adaptation and Treatment. 2017 Aug 9; 13–26.
References
Anti-BLV antibodies in whey correlate with bovine leukemia virus disease progression and BoLA-DRB3 polymorphism
Front Vet Sci
Authors: Nakatsuchi A, Bao A, Watanuki S, Matsuura R, Borjigin L, Bai L, Kuroda M, Matsumoto Y, Kohara J, Aida Y.
Abstract
Introduction: Bovine leukemia virus (BLV) belongs to the family Retroviridae and is a causative agent for enzootic bovine leucosis, the most common neoplastic disease affecting cattle worldwide. BLV proviral load (PVL) is associated with disease progression and transmission risk but requires blood collection and quantitative PCR testing. Anti-BLV antibodies in whey have been used as a diagnostic tool for BLV infection; however, quantitative utilization has not been fully investigated. Furthermore, bovine leukocyte antigen (BoLA)-DRB3 is a polymorphic gene associated with BLV infectivity and PVL, but its effect on anti-BLV antibody levels in whey from BLV infected dams is unknown. Therefore, we aimed to investigate whether it is possible to correctly predict PVL in the blood and milk based on the amount of anti-BLV antibodies in milk, and whether the BoLA-DRB3 alleles associate with the amount of anti-BLV antibodies in milk.
Methods: We examined whey from 442 dams from 11 different dairy farms located in 6 prefectures in Japan, including susceptible dams carrying at least one BoLA-DRB3* 012:01 or * 015:01 allele related with high PVL, resistant dams carrying at least one BoLA-DRB3 * 002:01, * 009:02, or * 014:01:01 allele related with low PVL, and neutral dams carrying other alleles.
Results: First, our results provided compelling evidence that anti-BLV antibody levels in whey were positively correlated with the anti-BLV antibody levels in serum and with BLV PVL in blood and milk, indicating the possibility of estimating BLV PVL in blood and milk by measuring anti-BLV antibody levels in whey. Thus, our results showed that antibody titers in milk might be effective for estimating BLV transmission risk and disease progression in the field. Second, we demonstrated that anti-BLV antibody levels in whey from BLV resistant dams were significantly lower than those from susceptible and neutral dams.
Discussion: This is the first report suggesting that the BoLA-DRB3 polymorphism affects anti-BLV antibody levels in whey from BLV-infected dams. Taken together, our results suggested that anti-BLV antibody levels in whey, measured by enzyme-linked immunosorbent assay, may be a useful marker to diagnose the risk of BLV infection and estimate PVL in blood and milk.
BLV-miR-B1-5p Promotes Staphylococcus aureus Adhesion to Mammary Epithelial Cells by Targeting MUC1
Animals (Basel)
Authors: Lian S, Liu P, Li X, Lv G, Song J, Zhang H, Wu R, Wang D, Wang J.
Abstract
Bovine leukemia virus (BLV) is widely prevalent worldwide and can persistently infect mammary epithelial cells in dairy cows, leading to reduced cellular antimicrobial capacity. BLV-encoded microRNAs (BLV-miRNAs) can modify host genes and promote BLV replication. We previously showed that BLV-miR-B1-5p significantly promoted Staphylococcus aureus (S. aureus) adhesion to bovine mammary epithelial (MAC-T) cells; however, the pathway responsible for this effect remained unclear. This study aims to examine how BLV-miR-B1-5p promotes S. aureus adhesion to MAC-T cells via miRNA target gene prediction and validation. Target site prediction showed that BLV-miR-B1-5p could target the mucin family gene mucin 1 (MUC1). Real-time polymerase chain reaction, immunofluorescence, and dual luciferase reporter assay further confirmed that BLV-miR-B1-5p could target and inhibit the expression of MUC1 in bovine MAC-T cells while interfering with the expression of MUC1 promoted S. aureus adhesion to MAC-T cells. These results indicate that BLV-miR-B1-5p promotes S. aureus adhesion to mammary epithelial cells by targeting MUC1.