Abstract
Bovine Leukemia Virus (BLV) is the etiological agent of enzootic bovine leucosis (EBL), a lymphoproliferative disease of the bovine species. In BLV-infected cells, the long terminal repeat (LTR), the viral Tax protein and viral miRNAs promote viral and cell proliferation as well as tumorigenesis. Although their respective roles are decisive in BLV biology, little is known about the genetic sequence variation of these parts of the BLV genome and their impact on disease outcome. Therefore, the objective of this study was to assess the relationship between disease progression and sequence variation of the BLV Tax, miRNA and LTR regions in infected animals displaying either low or high levels of persistent lymphocytosis (PL). A statistically significant association was observed between the A(+187)C polymorphism in the downstream activator sequence (DAS) region in LTR (p-value = 0.00737) and high lymphocytosis. Our study also showed that the mutation A(−4)G in the CAP site occurred in 70% of isolates with low PL and was not found in the high PL group. Conversely, the mutations G(−133)A/C in CRE2 (46.7%), C(+160)T in DAS (30%) and A(310)del in BLV-mir-B4-5p, A(357)G in BLV-mir-B4-3p, A(462)G in BLV-mir-B5-5p, and GA(497–498)AG in BLV-mir-B5-3p (26.5%) were often seen in isolates with high PL and did not occur in the low PL group. In conclusion, we found several significant polymorphisms among BLV genomic sequences in Russia that would explain a progression towards higher or lower lymphoproliferation. The data presented in this article enabled the classification between two different genotypes; however, clear association between genotypes and the PL development was not found.
Highlights
Bovine leukaemia virus (BLV), which belongs to the Retroviridae family and Deltaretrovirus genus, is the etiologic agent of enzootic bovine leucosis (EBL)
The cluster analysis classified and identified the two groups of blood samples, where 22 000 white blood cell (WBC) per μL was set as the threshold between the two groups (Table S1A,B)
High proviral loads have been associated with EBL progression [37,38,39] and have been conventionally used in several studies as a determining index to forecast the progress of the disease, thereby justifying its use in our study
Summary
Bovine leukaemia virus (BLV), which belongs to the Retroviridae family and Deltaretrovirus genus, is the etiologic agent of enzootic bovine leucosis (EBL). BLV infection is found throughout the world, but its prevalence varies in different geographic locations, remaining the highest in the Americas and Asia. In the Russian Federation, EBL is the most common infectious disease in cattle, accounting for 67.1% of all infectious diseases diagnosed in cattle [1]. In some regions of Russia, there has been a slight decrease in the number of EBL- and BLV-infected cattle. The epizootic situation in 28 of the 60 regions of Russia has not improved according to statistics from 2019 [2]. Following BLV infection, three stages in the disease progression can be identified:
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