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A member of Deltaretrovirus, bovine leukemia virus (BLV) has the potential to cause zoonotic disease and in animals can cause leukemia in beef and dairy cattle. The virus has been found to be closely related to human T-cell leukemia virus type 1 (HTLV1). The BLV genome consists of 8714 nucleotides and has the typical retroviral genome regions: LTR (promoter region), gag (group-specific antigen, capsid region), pol (polymerase, reverse transcription region, synthesizes a copy of the DNA for the BLV RNA genome), and env (envelope). Deltaretroviruses also have an additional region, tax (transactivation region of the X gene). This region can cause malignant transformation by inhibiting DNA repair and disrupting cell growth control mechanisms. The gag gene is highly conserved and consists of 1178 nucleotides encoding the polypeptide precursor Pr44. It is subsequently cleaved by BLV protease into three major non-glycosylated proteins (p12 nucleocapsid, p24 nucleotide, and p15 matrix). A region between the gag and pol genes encodes the viral protease p14 (pro gene). It is responsible for the post-translational maturation of BLV. The pol gene encodes the reverse transcriptase and integrase enzymes responsible for the reverse transcription and integration of BLV proviral DNA into the host genome, leading to lifelong infection. The BLV surface (SU) protein gp51 and the transmembrane (TM) protein gp30 contain recognition sites required for viral entry and mediate cell fusion. Although genomic and subgenomic transcripts of the 5'LTR are barely expressed, BLV abundantly expresses a set of RNA polymerase III-transcribed microRNAs (miRNAs), which are expressed not only in tumors but also in the non-symptomatic stages of infection. miRNAs have been shown to modify at least six target genes related to apoptosis, immunity, cell signaling, and oncogenesis.
Figure 1. Schematic structure of BLV
(Source: Marawan MA, et al. 2021)
The main host of BLV is cattle, but it can also infect other animals, such as sheep, buffalo, rabbits, mice and pigs. Its infection rate is very high in cattle, ranging from 39% to 100% in beef cattle and dairy cows. The transmission frequency of BLV in dairy cows was higher than that in beef cattle. It is reported that the serum prevalence rates of dairy cows and beef cattle are 40.9% and 28.7%, respectively. BLV can be transmitted in cattle by either horizontal or vertical routes, with important sources of infection being fresh blood, semen, saliva, breast milk and nasal secretions from BLV-positive cattle. Although BLV infects cattle readily, less than 5% of infected cattle develop disease.
BLV and BLV-infected cells are present in the colostrum and milk of most infected cows, which is the most likely route of BLV transmission from cattle to humans. One study found that the BLV genome and antibodies against the capsid protein can be found in blood samples from women.
BLV can infect different immune cells, among which the affinity to B lymphocytes is the highest. It exists in circulating peripheral blood B lymphocytes of cattle infected with BLV, but rarely in T cells. It disrupts the balance between B cells and T cells and changes their proliferation and apoptosis, because it interferes with gene expression and signal cascade at different stages after infection. Cows with persistent lymphocytosis will have a large number of B lymphocytes proliferation, these B lymphocytes surface expression of immunoglobulin and CD5+ antigens, prevent B lymphocyte apoptosis. The structural genes pol and env of BLV are critical for in vivo infectivity, and deletion of these two genes results in loss of infectivity. In addition, polymorphisms in the env gene cause changes in viral pathogenicity.
In the process of BLV infection, gp51 transmembrane glycoproteins together with fusion peptides destabilizes the host cell membrane, after which these structural proteins enhance viral fusion and infection of the host cell. Mutation of a single envelope N-linked glycosylation site of the env gene by conversion of the asparagine codon (N) to glutamate (E) enhances viral replication, fusion, and protein stability in experimentally infected sheep, thereby increasing the pathogenicity of BLV.
When the virus enters the body, it does not develop viremia. Instead, it induces a strong and long-lasting humoral immune response against structural proteins. BLV synthesizes proviral DNA by viral reverse transcriptase. The provirus is inserted randomly into the host genome in the infected nucleus by viral integrase. BLV proviruses can integrate into the genome of a cell without detection of the appropriate antibody and can infect the host for life. When this class of cells spreads to a new host, the BLV provirus is expressed as viral particles that infect other B lymphocytes.
According to the International Agency for Research on Cancer, infectious factors such as viruses are associated with 15%-20% of tumorigenesis and development. BLV can enter cells of different tissues through BLV receptors present on different types of cells. The tax genes in BLV have certain regulatory functions (transcriptional activators) that may be involved in transformation by inhibiting the DNA repair system and disrupting tumor suppressor genes, leading to oxidative cellular damage. This may be relevant to several cancer types such as lung and breast cancer.
The gene sequence for BLV has been identified in human breast cancers. In a PCR-based case-control study, 67 (59%) of 114 breast cancers were BLV-positive compared with 30 (29%) of 104 normal breast controls. The prevalence of BLV was increased in benign (19.6%), premalignant (34%), and malignant (57.4%) breast tissue. Some researchers have found a significant geographic correlation between breast cancer mortality and milk and beef consumption. Countries with high milk and beef consumption, such as the United States, the United Kingdom, and Australia, also have high rates of breast cancer, while countries with low beef and milk consumption, such as India, Japan, and South Korea, also have low rates of breast cancer. Lactose intolerant women have a much lower risk of breast cancer than others.
Table 1. Bovine leukemia virus and human breast cancer
| Breast specimens | Diagnosis | Non-cancer controls | Identification technique | Bovine Ieukemia virus positive breast cancer (%) | Bovine Ieukemia virus positive non-cancer controls (%) |
| Columbia | Invasive breast cancers | Benign breast tissues | Standard PCR | 19/53 (36%) | 24/53 (45%) |
| US | Invasive breast cancers | Normal breast tissues | In situ PCR | 67/114 (59%) | 30/104 (29%) |
| Australia | Invasive breast cancers | Benign breast tissues | In situ PCR | 40/50 (80%) | 19/46 (41%) |
| US | Invasive breast cancers | Benign breast tissues | In situ PCR | 35/61 (57%) | 20/103 (20%) |
| US | Invasive breast cancers | Normal breast tissues | Whole-genome sequencing | 0/51 | 0/19 |
(Source: Lawson JS, et al. 2018)
BLV and HTLV-1 integrate preferentially into the vicinity of cancer drivers and alter host gene expression by different mechanisms, including transcription of antisense chimeric virus-host RNA. During BLV-induced leukemogenesis, cis-interference of cancer drivers located in the vicinity of proviruses appears to be a major determinant of early clonal amplification.
References
| Target | Cat. No. | Product Name | Expression System | Tag/Conjugate | Application | |
| BLV | DAG-WT766 | Recombinant Bovine Leukemia Virus gp51 | Insect cells | TBD | N/A | Inquiry |
| Target | Cat. No. | Product Name | Host | Isotype | Application | |
| BLV | CABT-BL8921 | Anti-BLV gp51-G monoclonal antibody | Mouse | IgG1 | IP, WB, ELISA | Inquiry |
| CABT-BL8922 | Anti-BLV p24 monoclonal antibody | Mouse | IgG1 | RIPA, WB, ELISA, IAC | Inquiry | |
| BLV gp51 | CABT-RM001 | Mouse Anti-BLV gp51 D-D' monoclonal antibody, clone CMW3 | Mouse | IgG1 | RIPA, WB, FC, ELISA, IAC | Inquiry |
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