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Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice.
Silva-Filho, Joao Luiz; de Oliveira, Lilian G; Monteiro, Leticia; Parise, Pierina L; Zanluqui, Nagela G; Polonio, Carolina M; de Freitas, Carla L; Toledo-Teixeira, Daniel A; de Souza, William M; Bittencourt, Najara; Amorim, Mariene R; Forato, Julia; Muraro, Stéfanie P; de Souza, Gabriela F; Martini, Matheus C; Bispo-Dos-Santos, Karina; Vieira, Aline; Judice, Carla C; Pastore, Glaucia M; Amaral, Eliana; Passini Junior, Renato; Mayer-Milanez, Helaine M B P; Ribeiro-do-Valle, Carolina C; Calil, Roseli; Renato Bennini Junior, João; Lajos, Giuliane J; Altemani, Albina; Nolasco da Silva, Marcos T; Carolina Coan, Ana; Francisca Colella-Santos, Maria; von Zuben, Andrea P B; Vinolo, Marco Aurélio R; Arns, Clarice Weis; Catharino, Rodrigo Ramos; Costa, Maria Laura; Angerami, Rodrigo N; Freitas, André R R; Resende, Mariangela R; Garcia, Márcia T; Luiza Moretti, Maria; Renia, Laurent; Ng, Lisa F P; Rothlin, Carla V; Costa, Fabio T M; Peron, Jean Pierre Schatzmann; Proença-Modena, José Luiz.
Afiliación
  • Silva-Filho JL; Laboratory of Tropical Diseases Prof. Luiz Jacintho Silva, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil.
  • de Oliveira LG; Neuroimmune Interactions Laboratory, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, Brazil.
  • Monteiro L; Laboratory of Tropical Diseases Prof. Luiz Jacintho Silva, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil.
  • Parise PL; Laboratory of Emerging Viruses (LEVE), Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil.
  • Zanluqui NG; Neuroimmune Interactions Laboratory, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, Brazil.
  • Polonio CM; Neuroimmune Interactions Laboratory, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, Brazil.
  • de Freitas CL; Neuroimmune Interactions Laboratory, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, Brazil.
  • Toledo-Teixeira DA; Laboratory of Emerging Viruses (LEVE), Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil.
  • de Souza WM; Virology Research Center, Ribeirão Preto Medical School, University of São Paulo, Ribeirão Preto, Brazil; Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
  • Bittencourt N; Laboratory of Tropical Diseases Prof. Luiz Jacintho Silva, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil.
  • Amorim MR; Laboratory of Emerging Viruses (LEVE), Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil.
  • Forato J; Laboratory of Emerging Viruses (LEVE), Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil.
  • Muraro SP; Laboratory of Emerging Viruses (LEVE), Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil.
  • de Souza GF; Laboratory of Emerging Viruses (LEVE), Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil.
  • Martini MC; Laboratory of Emerging Viruses (LEVE), Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil.
  • Bispo-Dos-Santos K; Laboratory of Emerging Viruses (LEVE), Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil.
  • Vieira A; Laboratory of Emerging Viruses (LEVE), Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil.
  • Judice CC; Laboratory of Tropical Diseases Prof. Luiz Jacintho Silva, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil.
  • Pastore GM; Faculty of Food Engineering, UNICAMP, Brazil.
  • Amaral E; Department of Obstetrics and Gynecology, School of Medical Sciences, University of Campinas, Campinas. Brazil.
  • Passini Junior R; Department of Obstetrics and Gynecology, School of Medical Sciences, University of Campinas, Campinas. Brazil.
  • Mayer-Milanez HMBP; Department of Obstetrics and Gynecology, School of Medical Sciences, University of Campinas, Campinas. Brazil.
  • Ribeiro-do-Valle CC; Department of Obstetrics and Gynecology, School of Medical Sciences, University of Campinas, Campinas. Brazil.
  • Calil R; Department of Obstetrics and Gynecology, School of Medical Sciences, University of Campinas, Campinas. Brazil.
  • Renato Bennini Junior J; Department of Obstetrics and Gynecology, School of Medical Sciences, University of Campinas, Campinas. Brazil.
  • Lajos GJ; Department of Obstetrics and Gynecology, School of Medical Sciences, University of Campinas, Campinas. Brazil.
  • Altemani A; Department of Clinical Pathology, School of Medical Sciences, University of Campinas, Campinas, Brazil.
  • Nolasco da Silva MT; Pediatric Immunology, Center for Investigation in Pediatrics, Faculty of Medical Sciences, UNICAMP, Brazil.
  • Carolina Coan A; Department of Neurology, School of Medical Sciences, UNICAMP, Brazil.
  • Francisca Colella-Santos M; Department of Human Development and Rehabilitation, School of Medical Sciences, UNICAMP, Brazil.
  • von Zuben APB; Campinas Department of Public Health Surveillance, Campinas, Brazil.
  • Vinolo MAR; Department of Genetics, Microbiology and Immunology, Institute of Biology, UNICAMP, Brazil.
  • Arns CW; Department of Genetics, Microbiology and Immunology, Institute of Biology, UNICAMP, Brazil.
  • Catharino RR; School of Pharmaceutical Sciences, UNICAMP, Campinas, Brazil.
  • Costa ML; Department of Obstetrics and Gynecology, School of Medical Sciences, University of Campinas, Campinas. Brazil.
  • Angerami RN; Campinas Department of Public Health Surveillance, Campinas, Brazil; Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, SP, Brazil.
  • Freitas ARR; Campinas Department of Public Health Surveillance, Campinas, Brazil.
  • Resende MR; Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, SP, Brazil.
  • Garcia MT; Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, SP, Brazil.
  • Luiza Moretti M; Department of Internal Medicine, School of Medical Sciences, University of Campinas, Campinas, SP, Brazil.
  • Renia L; A*STAR Infectious Diseases Labs (A* ID Labs), Agency for Science, Technology and Research, Biopolis, Singapore; Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis, Singapore.
  • Ng LFP; A*STAR Infectious Diseases Labs (A* ID Labs), Agency for Science, Technology and Research, Biopolis, Singapore; Singapore Immunology Network, Agency for Science, Technology and Research, Biopolis, Singapore.
  • Rothlin CV; Department of Immunobiology, Yale University, School of Medicine, New Haven, CT, United States.
  • Costa FTM; Laboratory of Tropical Diseases Prof. Luiz Jacintho Silva, Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil. Electronic address: costaftm@unicamp.br.
  • Peron JPS; Neuroimmune Interactions Laboratory, Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, São Paulo, Brazil; Immunopathology and Allergy Post Graduate Program, School of Medicine, University of São Paulo, São Paulo, Brazil; Scientific Platform Pasteur-USP, University
  • Proença-Modena JL; Laboratory of Emerging Viruses (LEVE), Department of Genetics, Evolution, Microbiology and Immunology, Institute of Biology, University of Campinas, Campinas, Brazil; Experimental Medicine Research Cluster (EMRC), University of Campinas, Campinas, SP 13083-862, Brazil. Electronic address: jlmodena@u
Brain Behav Immun ; 97: 260-274, 2021 10.
Article en En | MEDLINE | ID: mdl-34390806
ABSTRACT
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 infection.
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Virus Zika / Infección por el Virus Zika / Enfermedades del Sistema Nervioso Límite: Animals / Female / Humans / Pregnancy Idioma: En Año: 2021 Tipo del documento: Article
Texto completo
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Texto completo: 1 Banco de datos: MEDLINE Asunto principal: Virus Zika / Infección por el Virus Zika / Enfermedades del Sistema Nervioso Límite: Animals / Female / Humans / Pregnancy Idioma: En Año: 2021 Tipo del documento: Article