Abstract:Bovine leukemia virus latency is a viral strategy used to escape from the host immune system and contribute to tumor development. However, a highly expressed BLV micro-RNA cluster has been reported, suggesting that the BLV silencing is not complete. Here, we demonstrate the in vivo recruitment of RNA polymerase III to the BLV miRNA cluster both in BLV-latently infected cell lines and in ovine BLV-infected primary cells, through a canonical type 2 RNAPIII promoter. Moreover, by RPC6-knockdown, we showed a direc… Show more
“…Viral miRNAs are strongly expressed in preleukemic and malignant cells, and may have roles in tumor onset and progression [ 39 , 40 ] through their effects on proviral load and consequently viral replication in the natural host [ 41 ]. Besides, Van Driessche et al revealed the recruitment of positive epigenetic marks on BLV miRNA cluster, inducing strong antisense promoter activity [ 42 ]. They also identified cis -acting elements of an RNAPII-dependent promoter [ 42 ].…”
Section: Introductionmentioning
confidence: 99%
“…Besides, Van Driessche et al revealed the recruitment of positive epigenetic marks on BLV miRNA cluster, inducing strong antisense promoter activity [ 42 ]. They also identified cis -acting elements of an RNAPII-dependent promoter [ 42 ]. Fig.…”
Bovine leukemia virus (BLV), an oncogenic member of the Deltaretrovirus genus, is closely related to human T-cell leukemia virus (HTLV-I and II). BLV infects cattle worldwide and causes important economic losses. In this review, we provide a summary of available information about commonly used diagnostic approaches for the detection of BLV infection, including both serological and viral genome-based methods. We also outline genotyping methods used for the phylogenetic analysis of BLV, including PCR restriction length polymorphism and modern DNA sequencing-based methods. In addition, detailed epidemiological information on the prevalence of BLV in cattle worldwide is presented. Finally, we summarize the various BLV genotypes identified by the phylogenetic analyses of the whole genome and env gp51 sequences of BLV strains in different countries and discuss the distribution of BLV genotypes worldwide.
“…Viral miRNAs are strongly expressed in preleukemic and malignant cells, and may have roles in tumor onset and progression [ 39 , 40 ] through their effects on proviral load and consequently viral replication in the natural host [ 41 ]. Besides, Van Driessche et al revealed the recruitment of positive epigenetic marks on BLV miRNA cluster, inducing strong antisense promoter activity [ 42 ]. They also identified cis -acting elements of an RNAPII-dependent promoter [ 42 ].…”
Section: Introductionmentioning
confidence: 99%
“…Besides, Van Driessche et al revealed the recruitment of positive epigenetic marks on BLV miRNA cluster, inducing strong antisense promoter activity [ 42 ]. They also identified cis -acting elements of an RNAPII-dependent promoter [ 42 ]. Fig.…”
Bovine leukemia virus (BLV), an oncogenic member of the Deltaretrovirus genus, is closely related to human T-cell leukemia virus (HTLV-I and II). BLV infects cattle worldwide and causes important economic losses. In this review, we provide a summary of available information about commonly used diagnostic approaches for the detection of BLV infection, including both serological and viral genome-based methods. We also outline genotyping methods used for the phylogenetic analysis of BLV, including PCR restriction length polymorphism and modern DNA sequencing-based methods. In addition, detailed epidemiological information on the prevalence of BLV in cattle worldwide is presented. Finally, we summarize the various BLV genotypes identified by the phylogenetic analyses of the whole genome and env gp51 sequences of BLV strains in different countries and discuss the distribution of BLV genotypes worldwide.
“…Recently, researchers discovered that the BLV genome encodes 5 pre-microRNA (miRNA) hairpins that produce 10 mature miRNAs in a genomic region previously thought to be inactive ( 15 , 16 ). BLV miRNAs are atypical in several ways; virally encoded miRNAs are unusual in RNA viruses due to the potential for cleaving genomic RNA ( 15 ) and BLV miRNAs are transcribed by RNA polymerase III (RNAPIII), as opposed to the typical miRNA biosynthesis that utilizes RNAPII ( 15 – 18 ). Despite these unusual features, BLV miRNAs have been detected at levels equivalent to endogenous miRNAs in both bovine B-cell tumors ( 16 ) and in experimentally infected bovine calves ( 19 ).…”
Bovine leukemia virus (BLV) is estimated to infect over 83% of dairy herds and over 40% of all dairy cows in the United States. While, BLV only causes leukemia in a small proportion of animals, research indicates that BLV+ cattle exhibit reduced milk production and longevity that is distinct from lymphoma development. It is hypothesized that BLV negatively affects production by interfering with cattle immunity and increasing the risk of secondary infections. In particular, BLV+ cows demonstrate reduced circulating levels of both antigen-specific and total IgM. This study investigated possible mechanisms by which BLV could interfere with the production of IgM in naturally infected cattle. Specifically, total plasma IgM and the expression of genes IGJ, BLIMP1, BCL6, and PAX5 in circulating IgM+ B cells were measured in 15 naturally infected BLV+ and 15 BLV− cows. In addition, BLV proviral load (PVL) (a relative measurement of BLV provirus integrated into host DNA) and the relative expression of BLV TAX and 5 BLV microRNAs (miRNAs) were characterized and correlated to the expression of selected endogenous genes. BLV+ cows exhibited lower total plasma IgM and lower expression of IGJ, BLIMP1, and BCL6. While, BLV TAX and BLV miRNAs failed to correlate with IGJ expression, both BLV TAX and BLV miRNAs exhibited negative associations with BLIMP1 and BCL6 gene expression. The results suggest a possible transcriptional pathway by which BLV interferes with IgM production in naturally infected cattle.
“…In contrast to 5′ LTR directed transcription, antisense RNA synthesis initiating at the 3′ LTR is consistently identified in primary ATL cells and BLV tumors ( Usui et al, 2008 ; Saito et al, 2009 ; Durkin et al, 2016 ). In contrast to HTLV-1, BLV also abundantly transcribes a cluster of microRNAs from internal pol III promoters ( Kincaid et al, 2012 ; Rosewick et al, 2013 ; Van Driessche et al, 2016 ). These microRNAs are required for efficient viral replication and induction of pathogenesis ( Gillet et al, 2016 ).…”
Section: Experimental Evidence and Interpretationsmentioning
In 1987, Mitsuaki Yoshida proposed the following model (Yoshida and Seiki, 1987): “... T-cells activated through the endogenous p40x would express viral antigens including the envelope glycoproteins which are exposed on the cell surface. These glycoproteins are targets of host immune surveillance, as is evidenced by the cytotoxic effects of anti-envelope antibodies or patient sera. Eventually all cells expressing the viral antigens, that is, all cells driven by the p40x would be rejected by the host. Only those cells that did not express the viral antigens would survive. Later, these antigen-negative infected cells would begin again to express viral antigens, including p40x, thus entering into the second cycle of cell propagation. These cycles would be repeated in so-called healthy virus carriers for 20 or 30 years or longer....” Three decades later, accumulated experimental facts particularly on intermittent viral transcription and regulation by the host immune response appear to prove that Yoshida was right. This Hypothesis and Theory summarizes the evidences that support this paradigm.
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