SV40 microRNA miR-S1-3p Downregulates the Expression of T Antigens to Control Viral DNA Replication, and TNFα and IL-17F Expression
Autor: | Takao Hijikata, Katsutoshi Yuasa, Misa Tokorodani, Tetsuyuki Takahashi, Hirona Ichikawa |
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Rok vydání: | 2020 |
Předmět: |
0301 basic medicine
Pharmacology DNA replication Pharmaceutical Science General Medicine Transfection Biology Cell biology 03 medical and health sciences 030104 developmental biology 0302 clinical medicine Plasmid Viral life cycle Viral replication Downregulation and upregulation 030220 oncology & carcinogenesis microRNA Tumor necrosis factor alpha |
Zdroj: | Biological and Pharmaceutical Bulletin. 43:1715-1728 |
ISSN: | 1347-5215 0918-6158 |
Popis: | SV40-encoded microRNA (miRNA), miR-S1, downregulates the large and small T antigens (LTag and STag), which promote viral replication and cellular transformation, thereby presumably impairing LTag and STag functions essential for the viral life cycle. To explore the functional significance of miR-S1-mediated downregulation of LTag and STag as well as the functional roles of miR-S1, we evaluated viral DNA replication and proinflammatory cytokine induction in cells transfected with simian virus 40 (SV40) genome plasmid and its mutated form lacking miR-S1 expression. The SV40 genome encodes two mature miR-S1s, miR-S1-3p and miR-S1-5p, of which miR-S1-3p is the predominantly expressed form. MiR-S1-3p exerted strong repressive effects on a reporter containing full-length sequence complementarity, but only marginal effect on one harboring a sequence complementary to its seed sequence. Consistently, miR-S1-3p downregulated LTag and STag transcripts with complete sequence complementarity through miR-S1-3p-Ago2-mediated mRNA decay. Transfection of SV40 plasmid induced higher DNA replication and lower LTag and STag transcripts in most of the examined cells compared to that miR-S1-deficient SV40 plasmid. However, miR-S1 itself did not affect DNA replication without the downregulation of LTag transcripts. Both LTag and STag induced the expression of tumor necrosis factor α (TNFα) and interleukin (IL)-17F, which was slightly reduced by miR-S1 due to miR-S1-mediated downregulation of LTag and STag. Forced miR-S1 expression did not affect TNFα expression, but increased IL-17F expression. Overall, our findings suggest that miR-S1-3p is a latent modifier of LTag and STag functions, ensuring efficient viral replication and attenuating cytokine expression detrimental to the viral life cycle. |
Databáze: | OpenAIRE |
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