| Author | Espada, Constanza Eleonora | |
| Author | Rocha, Edroaldo Lummertz | |
| Author | Ricciardi-Jorge, Taissa | |
| Author | Santos, Adara Aurea | |
| Author | Soares, Zamira Guerra | |
| Author | Malaquias, Greicy | |
| Author | Patrício, Daniel Oliveira | |
| Author | Kozlova, Edgar Gonzalez | |
| Author | Santos, Paula Fernandes | |
| Author | Bordignon, Juliano | |
| Author | Sanford, Thomas J | |
| Author | Fajardo, Teodoro | |
| Author | Sweeney, Trevor R | |
| Author | Báfica, André | |
| Author | Mansur, Daniel Santos | |
| Access date | 2024-12-10T14:53:01Z | |
| Available date | 2024-12-10T14:53:01Z | |
| Document date | 2024 | |
| Citation | ESPADA, C. E. et al. ISG15/USP18/STAT2 is a molecular hub regulating IFN I-mediated control of Dengue and Zika virus replication. Frontiers in Immunology, v. 15, n. 1331731, p. 01-14, 2024. | en_US |
| ISSN | 1664-3224 | en_US |
| URI | https://www.arca.fiocruz.br/handle/icict/67513 | |
| Description | The Supplementary Material for this article can be found online at: https://www.frontiersin.org/articles/10.3389/fimmu.2024.1331731/full#supplementary-material | en_US |
| Sponsorship | This work was supported by Comissão de Aperfeiçoamento de Pessoal de Nıvel Superior (CAPES) Computational Biology programme ́(23038.010048/2013-27), Conselho Nacional de Desenvolvimento Cientıfí co e Tecnológico (CNPq) (311406/2017-3 and 407609/2018-0), INCT Vacinas/CNPq and the Academy of Medical Sciences/U.K. (NAF004/1005) to DM. Howard Hughes Medical Institute – Early Career Scientist to AB. (55007412), Wellcome Trust and Royal Society Sir Henry Dale Fellowship (202471/Z/16/Z) to TS. Wellcome Trust PhD Studentship (105389/Z/14/Z) to TS. CAPES scholarship (88887.195782/2018-00) to ER. CNPq scholarship (205096/2018-2) to JB. | en_US |
| Language | eng | en_US |
| Publisher | Frontiers | en_US |
| Rights | open access | en_US |
| Subject in Portuguese | Vírus Dengue | en_US |
| Subject in Portuguese | Vírus Zika | en_US |
| Subject in Portuguese | Interferon tipo I | en_US |
| Subject in Portuguese | Resposta antiviral | en_US |
| Subject in Portuguese | Evasão imune | en_US |
| Title | ISG15/USP18/STAT2 is a molecular hub regulating IFN I-mediated control of Dengue and Zika virus replication | en_US |
| Type | Article | en_US |
| DOI | 10.3389/fimmu.2024.1331731 | |
| Abstract | The establishment of a virus infection is the result of the pathogen's ability to replicate in a hostile environment generated by the host's immune system. Here, we found that ISG15 restricts Dengue and Zika viruses' replication through the stabilization of its binding partner USP18. ISG15 expression was necessary to control DV replication driven by both autocrine and paracrine type one interferon (IFN-I) signaling. Moreover, USP18 competes with NS5-mediated STAT2 degradation, a major mechanism for establishment of flavivirus infection. Strikingly, reconstitution of USP18 in ISG15-deficient cells was sufficient to restore the STAT2's stability and restrict virus growth, suggesting that the IFNAR-mediated ISG15 activity is also antiviral. Our results add a novel layer of complexity in the virus/host interaction interface and suggest that NS5 has a narrow window of opportunity to degrade STAT2, therefore suppressing host's IFN-I mediated response and promoting virus replication. | en_US |
| Affilliation | Universidade Federal de Santa Catarina. Centro de Ciências Biológicas. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Imunobiologia. Florianópolis, SC, Brasil. | en_US |
| Affilliation | Universidade Federal de Santa Catarina. Centro de Ciências Biológicas. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Imunobiologia. Florianópolis, SC, Brasil. | en_US |
| Affilliation | Universidade Federal de Santa Catarina. Centro de Ciências Biológicas. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Imunobiologia. Florianópolis, SC, Brasil. | en_US |
| Affilliation | Universidade Federal de Santa Catarina. Centro de Ciências Biológicas. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Imunobiologia. Florianópolis, SC, Brasil. | en_US |
| Affilliation | Universidade Federal de Santa Catarina. Centro de Ciências Biológicas. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Imunobiologia. Florianópolis, SC, Brasil. | en_US |
| Affilliation | Universidade Federal de Santa Catarina. Centro de Ciências Biológicas. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Imunobiologia. Florianópolis, SC, Brasil. | en_US |
| Affilliation | Universidade Federal de Santa Catarina. Centro de Ciências Biológicas. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Imunobiologia. Florianópolis, SC, Brasil. | en_US |
| Affilliation | Universidade Federal de Santa Catarina. Centro de Ciências Biológicas. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Imunobiologia. Florianópolis, SC, Brasil. | en_US |
| Affilliation | Universidade Federal de Santa Catarina. Centro de Ciências Biológicas. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Imunobiologia. Florianópolis, SC, Brasil. | en_US |
| Affilliation | Fundação Oswaldo Cruz. Instituto Carlos Chagas. Laboratório de Virologia Molecular. Curitiba, PR, Brasil. | en_US |
| Affilliation | University of Cambridge. Addenbrooke’s Hospital. Department of Pathology. Division of Virology. Cambridge, United Kingdom. | en_US |
| Affilliation | University of Cambridge. Addenbrooke’s Hospital. Department of Pathology. Division of Virology. Cambridge, United Kingdom. | en_US |
| Affilliation | University of Cambridge. Addenbrooke’s Hospital. Department of Pathology. Division of Virology. Cambridge, United Kingdom / The Pirbright Institute. Viral Gene Expression Group. Guildford, United Kingdom. | en_US |
| Affilliation | Universidade Federal de Santa Catarina. Centro de Ciências Biológicas. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Imunobiologia. Florianópolis, SC, Brasil. | en_US |
| Affilliation | Universidade Federal de Santa Catarina. Centro de Ciências Biológicas. Departamento de Microbiologia, Imunologia e Parasitologia. Laboratório de Imunobiologia. Florianópolis, SC, Brasil. | en_US |
| Subject | Dengue virus | en_US |
| Subject | Zika virus | en_US |
| Subject | ISG15 | en_US |
| Subject | USP18 | en_US |
| Subject | Type one interferon | en_US |
| Subject | ISGylation | en_US |
| Subject | Antiviral response | en_US |
| Subject | Immune evasion | en_US |
| DeCS | Vírus da Dengue | en_US |
| DeCS | Vírus Zika | en_US |
| DeCS | Interferon-alfa | en_US |
