Abstract
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 non-coding 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.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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B-Lymphocytes* / metabolism
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B-Lymphocytes* / pathology
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B-Lymphocytes* / virology
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Cattle
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Cell Proliferation
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Cell Transformation, Viral*
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Leukemia Virus, Bovine* / genetics
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Leukemia Virus, Bovine* / metabolism
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Leukemia Virus, Bovine* / pathogenicity
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MicroRNAs* / genetics
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MicroRNAs* / metabolism
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RNA, Antisense* / genetics
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RNA, Antisense* / metabolism
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RNA, Viral* / genetics
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RNA, Viral* / metabolism
Substances
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MicroRNAs
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RNA, Antisense
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RNA, Viral
Grants and funding
This work was supported by the Belgian National Fund for Scientific Research (FNRS T006014 and T026120), the Belgian Foundation against Cancer, the Télévie and the “Fondation Léon Fredericq”. RS is a fellow of the Belgian Foundation against Cancer and the Télévie. LW is research director of the FNRS. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.