The Virus-Induced Upregulation of the miR-183/96/182 Cluster and the FoxO Family Protein Members Are Not Required for Efficient Replication of HSV-1
Herpes simplex virus 1 (HSV-1) expresses a large number of miRNAs, and their function is still not completely understood. In addition, HSV-1 has been found to deregulate host miRNAs, which adds to the complexity of the regulation of efficient virus replication. In this study, we comprehensively addr...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2022-07-01
|
| Series: | Viruses |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1999-4915/14/8/1661 |
| _version_ | 1827597977766592512 |
|---|---|
| author | Andreja Zubković Ines Žarak Ivana Ratkaj Filip Rokić Maja Jekić Marina Pribanić Matešić Ricardo Lebrón Cristina Gómez-Martín Berislav Lisnić Vanda Juranić Lisnić Stipan Jonjić Dongli Pan Oliver Vugrek Michael Hackenberg Igor Jurak |
| author_facet | Andreja Zubković Ines Žarak Ivana Ratkaj Filip Rokić Maja Jekić Marina Pribanić Matešić Ricardo Lebrón Cristina Gómez-Martín Berislav Lisnić Vanda Juranić Lisnić Stipan Jonjić Dongli Pan Oliver Vugrek Michael Hackenberg Igor Jurak |
| author_sort | Andreja Zubković |
| collection | DOAJ |
| description | Herpes simplex virus 1 (HSV-1) expresses a large number of miRNAs, and their function is still not completely understood. In addition, HSV-1 has been found to deregulate host miRNAs, which adds to the complexity of the regulation of efficient virus replication. In this study, we comprehensively addressed the deregulation of host miRNAs by massive-parallel sequencing. We found that only miRNAs expressed from a single cluster, miR-183/96/182, are reproducibly deregulated during productive infection. These miRNAs are predicted to regulate a great number of potential targets involved in different cellular processes and have only 33 shared targets. Among these, members of the FoxO family of proteins were identified as potential targets for all three miRNAs. However, our study shows that the upregulated miRNAs do not affect the expression of FoxO proteins, moreover, these proteins were upregulated in HSV-1 infection. Furthermore, we show that the individual FoxO proteins are not required for efficient HSV-1 replication. Taken together, our results indicate a complex and redundant response of infected cells to the virus infection that is efficiently inhibited by the virus. |
| first_indexed | 2024-03-09T03:43:00Z |
| format | Article |
| id | doaj.art-fa32aef653174c988e5e3c7d95c38545 |
| institution | Directory Open Access Journal |
| issn | 1999-4915 |
| language | English |
| last_indexed | 2024-03-09T03:43:00Z |
| publishDate | 2022-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Viruses |
| spelling | doaj.art-fa32aef653174c988e5e3c7d95c385452023-12-03T14:38:54ZengMDPI AGViruses1999-49152022-07-01148166110.3390/v14081661The Virus-Induced Upregulation of the miR-183/96/182 Cluster and the FoxO Family Protein Members Are Not Required for Efficient Replication of HSV-1Andreja Zubković0Ines Žarak1Ivana Ratkaj2Filip Rokić3Maja Jekić4Marina Pribanić Matešić5Ricardo Lebrón6Cristina Gómez-Martín7Berislav Lisnić8Vanda Juranić Lisnić9Stipan Jonjić10Dongli Pan11Oliver Vugrek12Michael Hackenberg13Igor Jurak14Department of Biotechnology, University of Rijeka, 51000 Rijeka, CroatiaDepartment of Biotechnology, University of Rijeka, 51000 Rijeka, CroatiaDepartment of Biotechnology, University of Rijeka, 51000 Rijeka, CroatiaLaboratory for Advanced Genomics, Rudjer Boskovic Institute, 10000 Zagreb, CroatiaDepartment of Biotechnology, University of Rijeka, 51000 Rijeka, CroatiaDepartment of Biotechnology, University of Rijeka, 51000 Rijeka, CroatiaGenetics Department & Biotechnology Institute, Biomedical Research Center (CIBM), University of Granada, 18100 Granada, SpainGenetics Department & Biotechnology Institute, Biomedical Research Center (CIBM), University of Granada, 18100 Granada, SpainCenter for Proteomics, Faculty of Medicine, University of Rijeka, 51000 Rijeka, CroatiaCenter for Proteomics, Faculty of Medicine, University of Rijeka, 51000 Rijeka, CroatiaCenter for Proteomics, Faculty of Medicine, University of Rijeka, 51000 Rijeka, CroatiaDepartment of Medical Microbiology and Parasitology, Zhejiang University School of Medicine, Hangzhou 310058, ChinaLaboratory for Advanced Genomics, Rudjer Boskovic Institute, 10000 Zagreb, CroatiaGenetics Department & Biotechnology Institute, Biomedical Research Center (CIBM), University of Granada, 18100 Granada, SpainDepartment of Biotechnology, University of Rijeka, 51000 Rijeka, CroatiaHerpes simplex virus 1 (HSV-1) expresses a large number of miRNAs, and their function is still not completely understood. In addition, HSV-1 has been found to deregulate host miRNAs, which adds to the complexity of the regulation of efficient virus replication. In this study, we comprehensively addressed the deregulation of host miRNAs by massive-parallel sequencing. We found that only miRNAs expressed from a single cluster, miR-183/96/182, are reproducibly deregulated during productive infection. These miRNAs are predicted to regulate a great number of potential targets involved in different cellular processes and have only 33 shared targets. Among these, members of the FoxO family of proteins were identified as potential targets for all three miRNAs. However, our study shows that the upregulated miRNAs do not affect the expression of FoxO proteins, moreover, these proteins were upregulated in HSV-1 infection. Furthermore, we show that the individual FoxO proteins are not required for efficient HSV-1 replication. Taken together, our results indicate a complex and redundant response of infected cells to the virus infection that is efficiently inhibited by the virus.https://www.mdpi.com/1999-4915/14/8/1661herpes simplex virus 1HSV-1virus-host interactionmiRNAFoxO |
| spellingShingle | Andreja Zubković Ines Žarak Ivana Ratkaj Filip Rokić Maja Jekić Marina Pribanić Matešić Ricardo Lebrón Cristina Gómez-Martín Berislav Lisnić Vanda Juranić Lisnić Stipan Jonjić Dongli Pan Oliver Vugrek Michael Hackenberg Igor Jurak The Virus-Induced Upregulation of the miR-183/96/182 Cluster and the FoxO Family Protein Members Are Not Required for Efficient Replication of HSV-1 Viruses herpes simplex virus 1 HSV-1 virus-host interaction miRNA FoxO |
| title | The Virus-Induced Upregulation of the miR-183/96/182 Cluster and the FoxO Family Protein Members Are Not Required for Efficient Replication of HSV-1 |
| title_full | The Virus-Induced Upregulation of the miR-183/96/182 Cluster and the FoxO Family Protein Members Are Not Required for Efficient Replication of HSV-1 |
| title_fullStr | The Virus-Induced Upregulation of the miR-183/96/182 Cluster and the FoxO Family Protein Members Are Not Required for Efficient Replication of HSV-1 |
| title_full_unstemmed | The Virus-Induced Upregulation of the miR-183/96/182 Cluster and the FoxO Family Protein Members Are Not Required for Efficient Replication of HSV-1 |
| title_short | The Virus-Induced Upregulation of the miR-183/96/182 Cluster and the FoxO Family Protein Members Are Not Required for Efficient Replication of HSV-1 |
| title_sort | virus induced upregulation of the mir 183 96 182 cluster and the foxo family protein members are not required for efficient replication of hsv 1 |
| topic | herpes simplex virus 1 HSV-1 virus-host interaction miRNA FoxO |
| url | https://www.mdpi.com/1999-4915/14/8/1661 |
| work_keys_str_mv | AT andrejazubkovic thevirusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT ineszarak thevirusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT ivanaratkaj thevirusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT filiprokic thevirusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT majajekic thevirusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT marinapribanicmatesic thevirusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT ricardolebron thevirusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT cristinagomezmartin thevirusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT berislavlisnic thevirusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT vandajuraniclisnic thevirusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT stipanjonjic thevirusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT donglipan thevirusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT olivervugrek thevirusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT michaelhackenberg thevirusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT igorjurak thevirusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT andrejazubkovic virusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT ineszarak virusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT ivanaratkaj virusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT filiprokic virusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT majajekic virusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT marinapribanicmatesic virusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT ricardolebron virusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT cristinagomezmartin virusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT berislavlisnic virusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT vandajuraniclisnic virusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT stipanjonjic virusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT donglipan virusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT olivervugrek virusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT michaelhackenberg virusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 AT igorjurak virusinducedupregulationofthemir18396182clusterandthefoxofamilyproteinmembersarenotrequiredforefficientreplicationofhsv1 |