Functional Analyses of Bovine Foamy Virus-Encoded miRNAs Reveal the Importance of a Defined miRNA for Virus Replication and Host–Virus Interaction
In addition to regulatory or accessory proteins, some complex retroviruses gain a repertoire of micro-RNAs (miRNAs) to regulate and control virus–host interactions for efficient replication and spread. In particular, bovine and simian foamy viruses (BFV and SFV) have recently been shown to express a...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-11-01
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| Series: | Viruses |
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| Online Access: | https://www.mdpi.com/1999-4915/12/11/1250 |
| _version_ | 1797549044900298752 |
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| author | Wenhu Cao Erik Stricker Agnes Hotz-Wagenblatt Anke Heit-Mondrzyk Georgios Pougialis Annette Hugo Jacek Kuźmak Magdalena Materniak-Kornas Martin Löchelt |
| author_facet | Wenhu Cao Erik Stricker Agnes Hotz-Wagenblatt Anke Heit-Mondrzyk Georgios Pougialis Annette Hugo Jacek Kuźmak Magdalena Materniak-Kornas Martin Löchelt |
| author_sort | Wenhu Cao |
| collection | DOAJ |
| description | In addition to regulatory or accessory proteins, some complex retroviruses gain a repertoire of micro-RNAs (miRNAs) to regulate and control virus–host interactions for efficient replication and spread. In particular, bovine and simian foamy viruses (BFV and SFV) have recently been shown to express a diverse set of RNA polymerase III-directed miRNAs, some with a unique primary miRNA double-hairpin, dumbbell-shaped structure not known in other viruses or organisms. While the mechanisms of expression and structural requirements have been studied, the functional importance of these miRNAs is still far from understood. Here, we describe the in silico identification of BFV miRNA targets and the subsequent experimental validation of bovine Ankyrin Repeat Domain 17 (ANKRD17) and Bax-interacting factor 1 (Bif1) target genes in vitro and, finally, the suppression of ANKRD17 downstream genes in the affected pathway. Deletion of the entire miRNA cassette in the non-coding part of the U3 region of the long terminal repeats attenuated replication of corresponding BFV mutants in bovine cells. This repression can be almost completely trans-complemented by the most abundant miRNA BF2-5p having the best scores for predicted and validated BFV miRNA target genes. Deletion of the miRNA cassette does not grossly affect particle release and overall particle composition. |
| first_indexed | 2024-03-10T15:09:04Z |
| format | Article |
| id | doaj.art-7175d9456c9244d798bcd22d81f73b4d |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-10T15:09:04Z |
| publishDate | 2020-11-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-7175d9456c9244d798bcd22d81f73b4d2023-11-20T19:32:13ZengMDPI AGViruses1999-49152020-11-011211125010.3390/v12111250Functional Analyses of Bovine Foamy Virus-Encoded miRNAs Reveal the Importance of a Defined miRNA for Virus Replication and Host–Virus InteractionWenhu Cao0Erik Stricker1Agnes Hotz-Wagenblatt2Anke Heit-Mondrzyk3Georgios Pougialis4Annette Hugo5Jacek Kuźmak6Magdalena Materniak-Kornas7Martin Löchelt8Division Viral Transformation Mechanisms, Research Focus Infection, Inflammation and Cancer, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), 69120 Heidelberg, GermanyDivision Viral Transformation Mechanisms, Research Focus Infection, Inflammation and Cancer, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), 69120 Heidelberg, GermanyCore Facility Omics IT and Data Management, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), 69120 Heidelberg, GermanyCore Facility Omics IT and Data Management, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), 69120 Heidelberg, GermanyDivision Viral Transformation Mechanisms, Research Focus Infection, Inflammation and Cancer, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), 69120 Heidelberg, GermanyDivision Viral Transformation Mechanisms, Research Focus Infection, Inflammation and Cancer, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), 69120 Heidelberg, GermanyDepartment of Biochemistry, National Veterinary Research Institute, 24–100 Pulawy, PolandDepartment of Biochemistry, National Veterinary Research Institute, 24–100 Pulawy, PolandDivision Viral Transformation Mechanisms, Research Focus Infection, Inflammation and Cancer, German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), 69120 Heidelberg, GermanyIn addition to regulatory or accessory proteins, some complex retroviruses gain a repertoire of micro-RNAs (miRNAs) to regulate and control virus–host interactions for efficient replication and spread. In particular, bovine and simian foamy viruses (BFV and SFV) have recently been shown to express a diverse set of RNA polymerase III-directed miRNAs, some with a unique primary miRNA double-hairpin, dumbbell-shaped structure not known in other viruses or organisms. While the mechanisms of expression and structural requirements have been studied, the functional importance of these miRNAs is still far from understood. Here, we describe the in silico identification of BFV miRNA targets and the subsequent experimental validation of bovine Ankyrin Repeat Domain 17 (ANKRD17) and Bax-interacting factor 1 (Bif1) target genes in vitro and, finally, the suppression of ANKRD17 downstream genes in the affected pathway. Deletion of the entire miRNA cassette in the non-coding part of the U3 region of the long terminal repeats attenuated replication of corresponding BFV mutants in bovine cells. This repression can be almost completely trans-complemented by the most abundant miRNA BF2-5p having the best scores for predicted and validated BFV miRNA target genes. Deletion of the miRNA cassette does not grossly affect particle release and overall particle composition.https://www.mdpi.com/1999-4915/12/11/1250bovine foamy virusspumaretrovirusmiRNA expressionvirus-host-interactionmiRNA target gene identificationinnate immunity |
| spellingShingle | Wenhu Cao Erik Stricker Agnes Hotz-Wagenblatt Anke Heit-Mondrzyk Georgios Pougialis Annette Hugo Jacek Kuźmak Magdalena Materniak-Kornas Martin Löchelt Functional Analyses of Bovine Foamy Virus-Encoded miRNAs Reveal the Importance of a Defined miRNA for Virus Replication and Host–Virus Interaction Viruses bovine foamy virus spumaretrovirus miRNA expression virus-host-interaction miRNA target gene identification innate immunity |
| title | Functional Analyses of Bovine Foamy Virus-Encoded miRNAs Reveal the Importance of a Defined miRNA for Virus Replication and Host–Virus Interaction |
| title_full | Functional Analyses of Bovine Foamy Virus-Encoded miRNAs Reveal the Importance of a Defined miRNA for Virus Replication and Host–Virus Interaction |
| title_fullStr | Functional Analyses of Bovine Foamy Virus-Encoded miRNAs Reveal the Importance of a Defined miRNA for Virus Replication and Host–Virus Interaction |
| title_full_unstemmed | Functional Analyses of Bovine Foamy Virus-Encoded miRNAs Reveal the Importance of a Defined miRNA for Virus Replication and Host–Virus Interaction |
| title_short | Functional Analyses of Bovine Foamy Virus-Encoded miRNAs Reveal the Importance of a Defined miRNA for Virus Replication and Host–Virus Interaction |
| title_sort | functional analyses of bovine foamy virus encoded mirnas reveal the importance of a defined mirna for virus replication and host virus interaction |
| topic | bovine foamy virus spumaretrovirus miRNA expression virus-host-interaction miRNA target gene identification innate immunity |
| url | https://www.mdpi.com/1999-4915/12/11/1250 |
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