Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice
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| Data de Publicação: | 2021 |
| Outros Autores: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Título da fonte: | Repositório da Produção Científica e Intelectual da Unicamp |
| Texto Completo: | https://hdl.handle.net/20.500.12733/2803 |
Resumo: | Agradecimentos: This study was financially supported by the São Paulo Research Foundation (FAPESP 2016/00194-8; 2017/26170-0 and 2017/22054-1); Biomedical Research Council (BMRC; core research grants provided to the Singapore Immunology Network); the BMRC A*STAR-led Zika Virus Consortium Fund (project 15/1/82/27/001); the Agency for Science, Technology and Research (A*STAR), Singapore. J.L.S.F., L. G.O., L.M., P.L.P., N.G.Z., C.M.P., D.A.T.-T., W.M.S., N.B., J.F., S.P.M., G.F.S. and K.B.-d.-S., received scholarship from FAPESP, grant numbers 2016/12855-9; 2016/21259-0; 2018/13866-0; 2017/02402-0, 2016/07371-2; 2017/11828-0; 2017/26908-0, 2017/22062-9, 2018/13645-3, 2020/02159-0 and 2020/02448-2, respectively. National Council for Scientific and Technological Development (CNPq) supported D.A.T.-T. and M.C.M., grant numbers 141844/2019-1 and 421724/2017-0. Fundo de Apoio ao Ensino, Pesquisa e Extens˜ao (FAEPEX) supported M.R.A., grant number 208/17. J.L.P.-M. was supported by CNPq grant number 305628/2020-8 |
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Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent miceZika virusInterferonTAM receptorsSocs1Congenital infectionArtigo originalAgradecimentos: This study was financially supported by the São Paulo Research Foundation (FAPESP 2016/00194-8; 2017/26170-0 and 2017/22054-1); Biomedical Research Council (BMRC; core research grants provided to the Singapore Immunology Network); the BMRC A*STAR-led Zika Virus Consortium Fund (project 15/1/82/27/001); the Agency for Science, Technology and Research (A*STAR), Singapore. J.L.S.F., L. G.O., L.M., P.L.P., N.G.Z., C.M.P., D.A.T.-T., W.M.S., N.B., J.F., S.P.M., G.F.S. and K.B.-d.-S., received scholarship from FAPESP, grant numbers 2016/12855-9; 2016/21259-0; 2018/13866-0; 2017/02402-0, 2016/07371-2; 2017/11828-0; 2017/26908-0, 2017/22062-9, 2018/13645-3, 2020/02159-0 and 2020/02448-2, respectively. National Council for Scientific and Technological Development (CNPq) supported D.A.T.-T. and M.C.M., grant numbers 141844/2019-1 and 421724/2017-0. Fundo de Apoio ao Ensino, Pesquisa e Extens˜ao (FAEPEX) supported M.R.A., grant number 208/17. J.L.P.-M. was supported by CNPq grant number 305628/2020-8Abstract: Zika virus (ZIKV) has the ability to cross placental and brain barriers, causing congenital malformations in neonates and neurological disorders in adults. However, the pathogenic mechanisms of ZIKV-induced neurological complications in adults and congenital malformations are still not fully understood. Gas6 is a soluble TAM receptor ligand able to promote flavivirus internalization and downregulation of immune responses. Here we demonstrate that there is a correlation between ZIKV neurological complications with higher Gas6 levels and the downregulation of genes associated with anti-viral response, as type I IFN due to Socs1 upregulation. Also, Gas6 gamma-carboxylation is essential for ZIKV invasion and replication in monocytes, the main source of this protein, which was inhibited by warfarin. Conversely, Gas6 facilitates ZIKV replication in adult immunocompetent mice and enabled susceptibility to transplacental infection. Our data indicate that ZIKV promotes the upregulation of its ligand Gas6, which contributes to viral infectivity and drives the development of severe adverse outcomes during ZIKV infectionFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESPCONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFechadoUNIVERSIDADE ESTADUAL DE CAMPINASSilva Filho, João Luiz daMonteiro, Letícia Cristina ScarapicchiaParise, Pierina Lorencini, 1995Toledo-Teixeira, Daniel Augusto de, 1993-Bittencourt, Najara Carneiro, 1990-Amorim, Mariene Ribeiro, 1992-Forato, Julia, 1996Muraro, Stéfanie PrimonSouza, Gabriela Ferreira de, 1991-Martini, Matheus Cavalheiro, 1983-Bispo-dos-Santos, Karina, 1993-Vieira, Aline, 1989-Judice, Carla Cristina, 1976-Pastore, Glaucia Maria, 1953-Amaral, Eliana Martorano, 1960-Passini Júnior, Renato, 1958-Mayer-Milanez, Helaine Maria Besteti, 1965-Ribeiro-do-Valle, Carolina Carvalho, 1983-Calil, RoseliBennini Junior, João Renato, 1978-Lajos, Giuliane Jesus, 1974-Altemani, Albina Messias de Almeida Milani, 1953-Silva, Marcos Tadeu Nolasco da, 1960-Coan, Ana Carolina, 1980-Colella-Santos, Maria Francisca, 1963-Von Zuben, Andrea Paula Bruno, 1974-Vinolo, Marco Aurélio Ramirez, 1982-Arns, Clarice Weis, 1956-Catharino, Rodrigo Ramos, 1977-Nascimento, Maria Laura Costa do, 1979-Angerami, Rodrigo NogueiraResende, Mariângela Ribeiro, 1966-Garcia, Márcia TeixeiraMoretti, Maria Luiza, 1953-Costa, Fabio Trindade Maranhão, 1972-Módena, José Luiz Proença, 1979-2021info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttps://hdl.handle.net/20.500.12733/2803SILVA FILHO, João Luiz da et al. Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice. Brain, behavior, and immunity. Philadelphia, PA: Elsevier, 2021. Vol. 97 (Oct., 2021), p. 260-274. Disponível em: https://hdl.handle.net/20.500.12733/2803. Acesso em: 24 mai. 2023.Inglêshttps://repositorio.unicamp.br/acervo/detalhe/1236129reponame:Repositório da Produção Científica e Intelectual da Unicampinstname:Universidade Estadual de Campinas (UNICAMP)instacron:UNICAMPinfo:eu-repo/semantics/openAccess2022-02-15T16:01:08Zoai:https://www.repositorio.unicamp.br/:1236129Repositório InstitucionalPUBhttp://repositorio.unicamp.br/oai/requestreposip@unicamp.bropendoar:2022-02-15T16:01:08Repositório da Produção Científica e Intelectual da Unicamp - Universidade Estadual de Campinas (UNICAMP)false |
| dc.title.none.fl_str_mv |
Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice |
| title |
Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice |
| spellingShingle |
Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice Silva Filho, João Luiz da Zika virus Interferon TAM receptors Socs1 Congenital infection Artigo original |
| title_short |
Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice |
| title_full |
Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice |
| title_fullStr |
Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice |
| title_full_unstemmed |
Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice |
| title_sort |
Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice |
| author |
Silva Filho, João Luiz da |
| author_facet |
Silva Filho, João Luiz da Monteiro, Letícia Cristina Scarapicchia Parise, Pierina Lorencini, 1995 Toledo-Teixeira, Daniel Augusto de, 1993- Bittencourt, Najara Carneiro, 1990- Amorim, Mariene Ribeiro, 1992- Forato, Julia, 1996 Muraro, Stéfanie Primon Souza, Gabriela Ferreira de, 1991- Martini, Matheus Cavalheiro, 1983- Bispo-dos-Santos, Karina, 1993- Vieira, Aline, 1989- Judice, Carla Cristina, 1976- Pastore, Glaucia Maria, 1953- Amaral, Eliana Martorano, 1960- Passini Júnior, Renato, 1958- Mayer-Milanez, Helaine Maria Besteti, 1965- Ribeiro-do-Valle, Carolina Carvalho, 1983- Calil, Roseli Bennini Junior, João Renato, 1978- Lajos, Giuliane Jesus, 1974- Altemani, Albina Messias de Almeida Milani, 1953- Silva, Marcos Tadeu Nolasco da, 1960- Coan, Ana Carolina, 1980- Colella-Santos, Maria Francisca, 1963- Von Zuben, Andrea Paula Bruno, 1974- Vinolo, Marco Aurélio Ramirez, 1982- Arns, Clarice Weis, 1956- Catharino, Rodrigo Ramos, 1977- Nascimento, Maria Laura Costa do, 1979- Angerami, Rodrigo Nogueira Resende, Mariângela Ribeiro, 1966- Garcia, Márcia Teixeira Moretti, Maria Luiza, 1953- Costa, Fabio Trindade Maranhão, 1972- Módena, José Luiz Proença, 1979- |
| author_role |
author |
| author2 |
Monteiro, Letícia Cristina Scarapicchia Parise, Pierina Lorencini, 1995 Toledo-Teixeira, Daniel Augusto de, 1993- Bittencourt, Najara Carneiro, 1990- Amorim, Mariene Ribeiro, 1992- Forato, Julia, 1996 Muraro, Stéfanie Primon Souza, Gabriela Ferreira de, 1991- Martini, Matheus Cavalheiro, 1983- Bispo-dos-Santos, Karina, 1993- Vieira, Aline, 1989- Judice, Carla Cristina, 1976- Pastore, Glaucia Maria, 1953- Amaral, Eliana Martorano, 1960- Passini Júnior, Renato, 1958- Mayer-Milanez, Helaine Maria Besteti, 1965- Ribeiro-do-Valle, Carolina Carvalho, 1983- Calil, Roseli Bennini Junior, João Renato, 1978- Lajos, Giuliane Jesus, 1974- Altemani, Albina Messias de Almeida Milani, 1953- Silva, Marcos Tadeu Nolasco da, 1960- Coan, Ana Carolina, 1980- Colella-Santos, Maria Francisca, 1963- Von Zuben, Andrea Paula Bruno, 1974- Vinolo, Marco Aurélio Ramirez, 1982- Arns, Clarice Weis, 1956- Catharino, Rodrigo Ramos, 1977- Nascimento, Maria Laura Costa do, 1979- Angerami, Rodrigo Nogueira Resende, Mariângela Ribeiro, 1966- Garcia, Márcia Teixeira Moretti, Maria Luiza, 1953- Costa, Fabio Trindade Maranhão, 1972- Módena, José Luiz Proença, 1979- |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
UNIVERSIDADE ESTADUAL DE CAMPINAS |
| dc.contributor.author.fl_str_mv |
Silva Filho, João Luiz da Monteiro, Letícia Cristina Scarapicchia Parise, Pierina Lorencini, 1995 Toledo-Teixeira, Daniel Augusto de, 1993- Bittencourt, Najara Carneiro, 1990- Amorim, Mariene Ribeiro, 1992- Forato, Julia, 1996 Muraro, Stéfanie Primon Souza, Gabriela Ferreira de, 1991- Martini, Matheus Cavalheiro, 1983- Bispo-dos-Santos, Karina, 1993- Vieira, Aline, 1989- Judice, Carla Cristina, 1976- Pastore, Glaucia Maria, 1953- Amaral, Eliana Martorano, 1960- Passini Júnior, Renato, 1958- Mayer-Milanez, Helaine Maria Besteti, 1965- Ribeiro-do-Valle, Carolina Carvalho, 1983- Calil, Roseli Bennini Junior, João Renato, 1978- Lajos, Giuliane Jesus, 1974- Altemani, Albina Messias de Almeida Milani, 1953- Silva, Marcos Tadeu Nolasco da, 1960- Coan, Ana Carolina, 1980- Colella-Santos, Maria Francisca, 1963- Von Zuben, Andrea Paula Bruno, 1974- Vinolo, Marco Aurélio Ramirez, 1982- Arns, Clarice Weis, 1956- Catharino, Rodrigo Ramos, 1977- Nascimento, Maria Laura Costa do, 1979- Angerami, Rodrigo Nogueira Resende, Mariângela Ribeiro, 1966- Garcia, Márcia Teixeira Moretti, Maria Luiza, 1953- Costa, Fabio Trindade Maranhão, 1972- Módena, José Luiz Proença, 1979- |
| dc.subject.por.fl_str_mv |
Zika virus Interferon TAM receptors Socs1 Congenital infection Artigo original |
| topic |
Zika virus Interferon TAM receptors Socs1 Congenital infection Artigo original |
| description |
Agradecimentos: This study was financially supported by the São Paulo Research Foundation (FAPESP 2016/00194-8; 2017/26170-0 and 2017/22054-1); Biomedical Research Council (BMRC; core research grants provided to the Singapore Immunology Network); the BMRC A*STAR-led Zika Virus Consortium Fund (project 15/1/82/27/001); the Agency for Science, Technology and Research (A*STAR), Singapore. J.L.S.F., L. G.O., L.M., P.L.P., N.G.Z., C.M.P., D.A.T.-T., W.M.S., N.B., J.F., S.P.M., G.F.S. and K.B.-d.-S., received scholarship from FAPESP, grant numbers 2016/12855-9; 2016/21259-0; 2018/13866-0; 2017/02402-0, 2016/07371-2; 2017/11828-0; 2017/26908-0, 2017/22062-9, 2018/13645-3, 2020/02159-0 and 2020/02448-2, respectively. National Council for Scientific and Technological Development (CNPq) supported D.A.T.-T. and M.C.M., grant numbers 141844/2019-1 and 421724/2017-0. Fundo de Apoio ao Ensino, Pesquisa e Extens˜ao (FAEPEX) supported M.R.A., grant number 208/17. J.L.P.-M. was supported by CNPq grant number 305628/2020-8 |
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2021 |
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2021 |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
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https://hdl.handle.net/20.500.12733/2803 SILVA FILHO, João Luiz da et al. Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice. Brain, behavior, and immunity. Philadelphia, PA: Elsevier, 2021. Vol. 97 (Oct., 2021), p. 260-274. Disponível em: https://hdl.handle.net/20.500.12733/2803. Acesso em: 24 mai. 2023. |
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SILVA FILHO, João Luiz da et al. Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice. Brain, behavior, and immunity. Philadelphia, PA: Elsevier, 2021. Vol. 97 (Oct., 2021), p. 260-274. Disponível em: https://hdl.handle.net/20.500.12733/2803. Acesso em: 24 mai. 2023. |
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Inglês |
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