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Bovine Leukemia Virus Small Noncoding RNAs Are Functional Elements That Regulate Replication and Contribute to Oncogenesis In Vivo
- Source :
- PLoS Pathogens, PLOS Pathogens 12(4) : e1005588 (2016), INTA Digital (INTA), Instituto Nacional de Tecnología Agropecuaria, instacron:INTA, PLoS Pathogens, Vol 12, Iss 4, p e1005588 (2016)
- Publication Year :
- 2015
-
Abstract
- Retroviruses are not expected to encode miRNAs because of the potential problem of self-cleavage of their genomic RNAs. This assumption has recently been challenged by experiments showing that bovine leukemia virus (BLV) encodes miRNAs from intragenomic Pol III promoters. The BLV miRNAs are abundantly expressed in B-cell tumors in the absence of significant levels of genomic and subgenomic viral RNAs. Using deep RNA sequencing and functional reporter assays, we show that miRNAs mediate the expression of genes involved in cell signaling, cancer and immunity. We further demonstrate that BLV miRNAs are essential to induce B-cell tumors in an experimental model and to promote efficient viral replication in the natural host.<br />Author Summary The recent discovery of miRNA expression by retroviruses is a matter of active debate and some controversy. Several retroviruses including human immunodeficiency virus (HIV) potentially encode functional small non-coding RNAs that are nevertheless undetectable in vivo. While these miRNAs regulate multiple host and viral processes in vitro, their contribution to infection and pathogenesis remains largely unknown. Using next-generation sequencing and reverse genetics, we provide mechanistic and functional evidence demonstrating that BLV miRNAs are functional genetic elements that regulate replication and contribute to oncogenesis in suitable animal models.
- Subjects :
- 0301 basic medicine
B Cells
Carcinogenesis
viruses
Artificial Gene Amplification and Extension
Virus Replication
Polymerase Chain Reaction
Biochemistry
Animal Diseases
White Blood Cells
Animal Cells
Virus Leucemia Bovina
Leukemia Virus, Bovine
Medicine and Health Sciences
lcsh:QH301-705.5
Subgenomic mRNA
Genetics
Regulation of gene expression
Mammals
Bovine leukemia virus
High-Throughput Nucleotide Sequencing
Agriculture
Ruminants
Complementary DNA
Oncogenicity
Enzymes
ARN
Nucleic acids
Cell Transformation, Neoplastic
Vertebrates
RNA, Viral
Cellular Types
Oxidoreductases
Luciferase
Research Article
lcsh:Immunologic diseases. Allergy
Gene Expression Regulation, Viral
Livestock
Forms of DNA
Immune Cells
Immunology
Biology
Enfermedades de los Animales
Research and Analysis Methods
Microbiology
RNA polymerase III
03 medical and health sciences
Extraction techniques
Virology
microRNA
Animals
Non-coding RNA
Molecular Biology Techniques
Antibody-Producing Cells
Gene
Oncogenicidad
Molecular Biology
Sheep
Blood Cells
Biology and life sciences
Gene Expression Profiling
Organisms
RNA
Proteins
DNA
Cell Biology
Enzootic Bovine Leukosis
biology.organism_classification
RNA extraction
Viral Replication
Gene regulation
MicroRNAs
030104 developmental biology
Viral replication
lcsh:Biology (General)
Amniotes
Enzymology
Bovine Leukaemia Virus
Parasitology
Cattle
Gene expression
lcsh:RC581-607
Subjects
Details
- ISSN :
- 15537374
- Volume :
- 12
- Issue :
- 4
- Database :
- OpenAIRE
- Journal :
- PLoS pathogens
- Accession number :
- edsair.doi.dedup.....f17de08f89a514725f344cec32e9641f