Bovine leukemia virus <i>pre-miRNA</i> genes<i>’</i> polymorphism

Zyrianova, Irina M.; Kovalchuk, Svetlana N.

doi:10.1080/15476286.2018.1555406

Cited by 8 publications

(13 citation statements)

References 45 publications

(60 reference statements)

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“…High levels of viral miRNAs are also found in the plasma of BLV-infected cows [24], suggesting a mechanism of paracrine signaling. Although polymorphisms were identified, the sequence of the miRNA cluster is well conserved among isolates, particularly in the seed region [20,22,25,26]. Target genes whose transcripts are affected by the miRNAs have been identified.…”

Section: Plos Pathogensmentioning

confidence: 99%

Ablation of non-coding RNAs affects bovine leukemia virus B lymphocyte proliferation and abrogates oncogenesis

et al. 2020

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Viruses have developed different strategies to escape from immune response. Among these, viral non-coding RNAs are invisible to the immune system and may affect the fate of the host cell. Bovine leukemia virus (BLV) encodes both short (miRNAs) and long (antisense AS1 and AS2) non-coding RNAs. To elucidate the mechanisms associated with BLV noncoding RNAs, we performed phenotypic and transcriptomic analyzes in a reverse genetics system. RNA sequencing of B-lymphocytes revealed that cell proliferation is the most significant mechanism associated with ablation of the viral non-coding RNAs. To assess the biological relevance of this observation, we determined the cell kinetic parameters in vivo using intravenous injection of BrdU and CFSE. Fitting the data to a mathematical model provided the rates of cell proliferation and death. Our data show that deletion of miRNAs correlates with reduced proliferation of the infected cell and lack of pathogenesis.

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Section: Plos Pathogensmentioning

confidence: 99%

Ablation of non-coding RNAs affects bovine leukemia virus B lymphocyte proliferation and abrogates oncogenesis

et al. 2020

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“…The BLV proviral genome has 8.7 kbp in length and includes structural genes (gag, pro, pol, and env) and non-structural ones (R3, G4, tax, rex, AS, pre-miRs (for miRNAs) [1,3,[7][8][9].…”

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confidence: 99%

Bovine leukemia virus tax gene/Tax protein polymorphism and its relation to Enzootic Bovine Leukosis

Zyrianova¹,

Kovalchuk²

2019

Virulence

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Bovine leukemia virus (BLV) is an oncogenic retrovirus of the Deltaretrovirus genus, which causes persistent infection in its natural hostscattle, zebu, and water buffalo with diverse clinical manifestations through the defeat of B-cells. The BLV proviral genome, along with structural genes (gag, pro, pol, and env), includes nonstructural ones (R3, G4, tax, rex, AS, pre-miRs (for miRNAs). We have shown in our previous data the association of some pre-miRs-B' (for BLV miRNA) alleles with leukocyte (WBCwhite blood cell) number in BLV-infected cows. Multifunctional properties of Tax protein have led us to an assumption that tax gene/Tax protein could have too population variations related to WBC counts. Here we report about several tax alleles/Tax protein variants, which have a highly significant association with an increase or a decrease of WBC number in BLV-infected cows. We have provided evidence that Tax A, H variants (tax b, c, d, f, e alleles) are correlated with reduced WBC counts at the level of BLV-negative groups of animals and thus could be the feature of the aleukemic (AL) form of BLV infection. We suggest this finding could be used in BLV testing for the presence of Tax A, H in the proviral DNA consider such strains of BLV as AL ones, and because of this, minimize the clinical losses due to BLV infection in cattle.

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“…We hypothesize that the above-described differences in Tax, miRNA and LTR sequences for BLV strains derived from cows with low and high lymphocytosis may suggest the existence of quasispecies. Such populations of proviral clones in individual cows with lymphocytosis have been identified for Tax and miRNA genes (so-called alleles) by Zyrianova et al [ 31 , 32 ]. It is noteworthy to mention that the presence of HTLV-1 quasispecies, as multiple infection, was also suggested in HTLV-1, which belong together with BLV to the Deltaretrovirus genus [ 63 , 64 ].…”

Section: Discussionmentioning

confidence: 99%

“…Another substitution, E(51)G, located in the putative zinc finger domain of Tax, is associated with increased white blood cell (WBC) count in BLV-infected cattle [ 31 ]. On the other hand, differences in WBC counts may depend on the presence of single nucleotide polymorphisms (SNPs) in BLV pre-miRNA genes (pre-miRNA-B2, -B3, -B4 and -B5) [ 32 ].…”

Section: Introductionmentioning

confidence: 99%

Analysis of Nucleotide Sequence of Tax, miRNA and LTR of Bovine Leukemia Virus in Cattle with Different Levels of Persistent Lymphocytosis in Russia

et al. 2021

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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 (−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.

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Bovine leukemia virus pre-miRNA genes’ polymorphism

Cited by 8 publications

References 45 publications

Ablation of non-coding RNAs affects bovine leukemia virus B lymphocyte proliferation and abrogates oncogenesis

Ablation of non-coding RNAs affects bovine leukemia virus B lymphocyte proliferation and abrogates oncogenesis

Bovine leukemia virus tax gene/Tax protein polymorphism and its relation to Enzootic Bovine Leukosis

Analysis of Nucleotide Sequence of Tax, miRNA and LTR of Bovine Leukemia Virus in Cattle with Different Levels of Persistent Lymphocytosis in Russia

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