Deep sequencing reveals abundant noncanonical retroviral microRNAs in B-cell leukemia/lymphoma

Rosewick, Nicolas; Momont, Mélanie; Durkin, Keith; Takeda, Hitoshi; Caiment, Florian; Cleuter, Yvette; Vernin, Céline; Mortreux, Franck; Wattel, Éric; Burny, Arsène; Georges, Michel; Broeke, Anne Van den

doi:10.1073/pnas.1213842110

Cited by 101 publications

(151 citation statements)

References 38 publications

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“…This finding may be against the traditional concept that RNA viruses generally do not encode miRNA; however, it is supported by several recent reports that RNA viruses are capable of expressing miRNA-like small RNAs [11][12][13][14]. By characterizing the genome sequence and possible structure of these miRNA-like small RNAs, our results further suggest that formation of hairpin structure may be a key step in biogenesis of miR-VP-3p.…”

supporting

confidence: 37%

An Ebola virus-encoded microRNA-like fragment serves as a biomarker for early diagnosis of Ebola virus disease

Chen

Liang²,

Chen³

et al. 2016

Cell Res

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supporting

confidence: 37%

An Ebola virus-encoded microRNA-like fragment serves as a biomarker for early diagnosis of Ebola virus disease

Chen

Liang²,

Chen³

et al. 2016

Cell Res

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“…Presumably, it is the second population which can form lymphomas as no provirus DNA expression is characteristic of tumor cells [8]. Recent accumulated data attest to the fact that the expression of BLV provirus microRNA found in the lymphocytes not expressing full BLV genome may be key factor to initiate neoplastic transformation of B cells [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

The Infection Hazard of Carriers of Proviral Bovine Leukemia Virus and Its Evaluation With Regard to Leukocytosis

Kosovskii¹,

Glazko²,

Andreichenko³

et al. 2016

S-h. biol.

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A b s t r a c tThe spread of the bovine leukemia virus (BLV) brings significant economic damage to dairy and beef cattle still due to the problems to develop the optimal methods for its prevention. The situation is compounded by the fact that the clinical manifestation of lymphocytic leukemia has been observed in animals during 5 to 10 years after infection in approximately 5-7 % of animals. Subdivision of BLV infected B cells on the producers of mature viral particles and precursors of the formation of lymphomas necessitates of separately consideration of the risk of infecting animals and forecast for development of lymphocytic leukemia. Testing antibodies to viral antigens, or provirus DNA insertion into the host genomes does not allow to reveal the most dangerous animals in view of their role in the infection spread, which is most essential for its control. In this regard, the particular urgency is the method development to assess the infection hazard from carriers of provirus DNA of bovine leukemia virus, associated with a large number of B lymphocytes, producing mature viral particles. In order to evaluate the possibility of using in these purposes not only testing individual animals on the quantity of viral RNA in blood samples, but the proliferative activity of leucocytes, these two characteristics were compared in the present work. The presence or absence of genome integrated provirus DNA in Black-and-White Holstein cows (n = 57, commercial herd) was evaluated and the group of infected animals was revealed when using primers designed by us for BLV gag and pol genes (G.Yu. Kosovoskii et al., 2013). The relative quantity expression of provirus in individual infected cows using RT-PCR analysis and primers to the fragment of the BLV pol gene were assessed. The counting of leukocytes in blood samples of all cows, included in the analysis, was performed. The number of leucocytes in cows free from infection, with the exception of one cow, was less than 1210 9 cells/l. This indicator in infected animals divided the investigated cows into two subgroupsin the first subgroup the leucocyte values did not exceed 1710 9 cells/l, in the second subgroup the number of leukocytes was significantly higher, reaching 2810 9 cells/l in some animals. It was important to note, that the amount (above 2010 9 cells/l) of BLV RNA, sufficient to detect by RT-PCR, was revealed only in the second subgroup. The coincidence of the increased leucocyte amount and the BLV RNA in blood of infected animals indicates that particular these cows represent the greatest infection hazard and suggests that the combination of estimates of the number of leukocytes and RNA BLV can be quite a reliable approach for the herd recovery by priority of their liquidation.

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“…In particular, herpesviruses generally express multiple viral miRNAs, especially in chronically infected cells, and polyomaand adenoviruses have also been shown to encode functional miRNAs. In contrast, analysis of numerous RNA viruses has so far failed to identify any viral miRNAs (5), with the exception of two retroviruses, i.e., bovine leukemia virus (BLV), which encodes five viral miRNAs (6,7), and an avian leucosis virus, termed ALV-J, which was recently shown to express a single viral miRNA in infected cells (8). One reason that RNA viruses might have only rarely evolved the ability to express miRNAs as a way of downregulating the expression of host genes with antiviral potential is that the excision of a pre-miRNA from a pri-miRNA precursor, likely the viral genomic RNA in the case of RNA viruses, would result in the cleavage of that pri-miRNA by Drosha.…”

mentioning

confidence: 99%

“…However, in this case, each viral miRNA is initially transcribed by RNA polymerase III (Pol III) as a pre-miRNA that is directly exported to the cytoplasm for Dicer cleavage (6,7). Importantly, while pre-miRNAs generally contain stems of ϳ22 bp, pri-miRNA stems are ϳ33 bp long, and Drosha cleavage is depen-dent on this longer stem length (11,12).…”

mentioning

confidence: 99%

Identification of Novel, Highly Expressed Retroviral MicroRNAs in Cells Infected by Bovine Foamy Virus

Whisnant

Kehl

Bao

et al. 2014

J Virol

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While numerous viral microRNAs (miRNAs) expressed by DNA viruses, especially herpesvirus family members, have been reported, there have been very few reports of miRNAs derived from RNA viruses. Here we describe three miRNAs expressed by bovine foamy virus (BFV), a member of the spumavirus subfamily of retroviruses, in both BFV-infected cultured cells and BFV-infected cattle. All three viral miRNAs are initially expressed in the form of an ϳ122-nucleotide (nt) pri-miRNA, encoded within the BFV long terminal repeat U3 region, that is subsequently cleaved to generate two pre-miRNAs that are then processed to yield three distinct, biologically active miRNAs. The BFV pri-miRNA is transcribed by RNA polymerase III, and the three resultant mature miRNAs were found to contribute a remarkable ϳ70% of all miRNAs expressed in BFV-infected cells. These data document the second example of a retrovirus that is able to express viral miRNAs by using embedded proviral RNA polymerase III promoters. IMPORTANCE Foamy viruses are a ubiquitous family of nonpathogenic retroviruses that have potential as gene therapy vectors in humans.Here we demonstrate that bovine foamy virus (BFV) expresses high levels of three viral microRNAs (miRNAs) in BFV-infected cells in culture and also in infected cattle. The BFV miRNAs are unusual in that they are initially transcribed by RNA polymerase III as a single, ϳ122-nt pri-miRNA that is subsequently processed to release three fully functional miRNAs. The observation that BFV, a foamy virus, is able to express viral miRNAs in infected cells adds to emerging evidence that miRNA expression is a common, albeit clearly not universal, property of retroviruses and suggests that these miRNAs may exert a significant effect on viral replication in vivo. M icroRNAs (miRNAs) are a diverse class of ϳ22-nucleotide (nt) regulatory RNAs that are expressed by all known multicellular eukaryotes (1). Cellular miRNAs are normally transcribed by RNA polymerase II (Pol II) to give rise to a long primiRNA that is cleaved in the nucleus by the microprocessor complex, consisting of the RNase III enzyme Drosha and the RNA-binding cofactor DGCR8, to release the ϳ60-nt pre-miRNA intermediate, which contains an ϳ22-bp imperfect stem with an ϳ2-nt 3= overhang (2). The pre-miRNA is then exported to the cytoplasm, where it is cleaved by a second RNase III enzyme, Dicer, which removes the terminal loop, leaving a second ϳ2-nt 3= overhang.

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Deep sequencing reveals abundant noncanonical retroviral microRNAs in B-cell leukemia/lymphoma

Cited by 101 publications

References 38 publications

An Ebola virus-encoded microRNA-like fragment serves as a biomarker for early diagnosis of Ebola virus disease

An Ebola virus-encoded microRNA-like fragment serves as a biomarker for early diagnosis of Ebola virus disease

The Infection Hazard of Carriers of Proviral Bovine Leukemia Virus and Its Evaluation With Regard to Leukocytosis

Identification of Novel, Highly Expressed Retroviral MicroRNAs in Cells Infected by Bovine Foamy Virus

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