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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice

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Author(s):
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Silva-Filho, Joao Luiz [1] ; de Oliveira, Lilian G. [2] ; Monteiro, Leticia [1] ; Parise, Pierina L. [3] ; Zanluqui, Nagela G. [2] ; Polonio, Carolina M. [2] ; de Freitas, Carla L. [2] ; Toledo-Teixeira, Daniel A. [3] ; de Souza, William M. [4, 5] ; Bittencourt, Najara [1] ; Amorim, Mariene R. [3] ; Forato, Julia [3] ; Muraro, Stefanie P. [3] ; de Souza, Gabriela F. [3] ; Martini, Matheus C. [3] ; Bispo-dos-Santos, Karina [3] ; Vieira, Aline [3] ; Judice, Carla C. [1] ; Pastore, Glaucia M. [6] ; Amaral, Eliana [7] ; Passini Junior, Renato [7] ; Mayer-Milanez, Helaine M. B. P. [7] ; Ribeiro-do-Valle, Carolina C. [7] ; Calil, Roseli [7] ; Bennini Junior, Joao Renato [7] ; Lajos, Giuliane J. [7] ; Altemani, Albina [8] ; Nolasco da Silva, Marcos T. [9] ; Coan, Ana Carolina [10] ; Colella-Santos, Maria Francisca [11] ; von Zuben, Andrea P. B. [12] ; Vinolo, Marco Aurelio R. [13] ; Arns, Clarice Weis [13] ; Catharino, Rodrigo Ramos [14] ; Costa, Maria Laura [7] ; Angerami, Rodrigo N. [15, 12] ; Freitas, Andre R. R. [12] ; Resende, Mariangela R. [15] ; Garcia, Marcia T. [15] ; Moretti, Maria Luiza [15] ; Renia, Laurent [16, 17] ; Ng, Lisa F. P. [16, 17] ; Rothlin, V, Carla ; Costa, Fabio T. M. [1] ; Schatzmann Peron, Jean Pierre [2, 18, 19] ; Proenca-Modena, Jose Luiz [20, 3]
Total Authors: 46
Affiliation:
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[1] Univ Estadual Campinas, Inst Biol, Dept Genet Evolut Microbiol & Immunol, Lab Trop Dis Prof Luiz Jacintho Silva, Campinas - Brazil
[2] Univ Sao Paulo, Inst Biomed Sci, Dept Immunol, Neuroimmune Interact Lab, Sao Paulo - Brazil
[3] Univ Estadual Campinas, Inst Biol, Dept Genet Evolut Microbiol & Immunol, Lab Emerging Viruses LEVE, Campinas - Brazil
[4] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 - USA
[5] Univ Sao Paulo, Virol Res Ctr, Ribeirao Preto Med Sch, Ribeirao Preto - Brazil
[6] Univ Estadual Campinas, Fac Food Engn, Campinas, SP - Brazil
[7] Univ Estadual Campinas, Sch Med Sci, Dept Obstet & Gynecol, Campinas - Brazil
[8] Univ Estadual Campinas, Sch Med Sci, Dept Clin Pathol, Campinas - Brazil
[9] Univ Estadual Campinas, Ctr Invest Pediat, Fac Med Sci, Pediat Immunol, Campinas, SP - Brazil
[10] Univ Estadual Campinas, Dept Neurol, Sch Med Sci, Campinas, SP - Brazil
[11] Univ Estadual Campinas, Dept Human Dev & Rehabil, Sch Med Sci, Campinas, SP - Brazil
[12] Campinas Dept Publ Hlth Surveillance, Campinas - Brazil
[13] Univ Estadual Campinas, Dept Genet Microbiol & Immunol, Inst Biol, Campinas, SP - Brazil
[14] Univ Estadual Campinas, Sch Pharmaceut Sci, Campinas - Brazil
[15] Univ Estadual Campinas, Sch Med Sci, Dept Internal Med, Campinas, SP - Brazil
[16] Agcy Sci Technol & Res, Biopolis, Singapore Immunol Network, Singapore - Singapore
[17] Agcy Sci Technol & Res, Biopolis, A Star Infect Dis Labs A ID Labs, Singapore - Singapore
[18] Univ Sao Paulo, Sch Med, Immunopathol & Allergy Post Grad Program, Sao Paulo - Brazil
[19] Univ Sao Paulo, Sci Platform Pasteur USP, Sao Paulo, SP - Brazil
[20] Univ Estadual Campinas, Expt Med Res Cluster EMRC, BR-13083862 Campinas, SP - Brazil
Total Affiliations: 20
Document type: Journal article
Source: BRAIN BEHAVIOR AND IMMUNITY; v. 97, p. 260-274, OCT 2021.
Web of Science Citations: 1
Abstract

Zika virus (ZIKV) has the ability to cross placental and brain barriers, causing congenital malformations in ne-onates 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. (AU)

FAPESP's process: 17/26908-0 - The role of IRF-5 in Oropouche virus pathogenesis and neurovirulence
Grantee:Pierina Lorencini Parise
Support type: Scholarships in Brazil - Doctorate (Direct)
FAPESP's process: 16/00194-8 - Pathogenesis and neurovirulence of emerging viruses in Brazil
Grantee:José Luiz Proença Módena
Support type: Research Grants - Young Investigators Grants
FAPESP's process: 20/02159-0 - Antiviral activity of AAK1 inhibitors against Oropouche infection
Grantee:Karina Bispo dos Santos
Support type: Scholarships in Brazil - Master
FAPESP's process: 16/21259-0 - The role of TAM receptors and their ligands, Gas6 and Pros 1 during infection by Zika virus in bone marrow-derived dendritic cells and macrophages of SJL and C57BL/6 mice
Grantee:Lilian Gomes de Oliveira
Support type: Scholarships in Brazil - Master
FAPESP's process: 18/13866-0 - Role of Gas6, ligand of TAM-type receptors, in the pathogenesis of Zika Virus infection in humans
Grantee:Letícia Cristina Scarapicchia Monteiro
Support type: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 16/12855-9 - Mechanism of action of lipoxin in the protection against experimental cerebral malaria
Grantee:João Luiz da Silva Filho
Support type: Scholarships in Brazil - Post-Doctorate
FAPESP's process: 17/22062-9 - Arbovirus detection and characterization in Campinas
Grantee:Julia Forato
Support type: Scholarships in Brazil - Technical Training Program - Technical Training
FAPESP's process: 17/26170-0 - Neuroimmunology in experimental models of Autoimmune Encephalomyelitis and Congenital Zika Syndrome: physiopathogenesis, susceptibility, cellular therapy, vaccination
Grantee:Jean Pierre Schatzmann Peron
Support type: Research Projects - Thematic Grants
FAPESP's process: 17/11828-0 - Evaluation of the microRNAs role in the immunopathogenesis of microcephaly caused by Zika virus in experimental models
Grantee:Carolina Manganeli Polonio
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 17/02402-0 - The role of adaptive immune response in neuroinvasion by Oropouche and Zika virus
Grantee:Daniel Augusto de Toledo Teixeira
Support type: Scholarships in Brazil - Master
FAPESP's process: 20/02448-2 - The role of the presence of IRF-5 in dendritic cells, macrophages and B lymphocytes to control infection by the Oropouche virus in murine model
Grantee:Camila Lopes Simeoni
Support type: Scholarships in Brazil - Scientific Initiation
FAPESP's process: 18/13645-3 - The role of innate recognition pathways and type I and III interferons in the rupture of the placental barrier after OROV infection
Grantee:Stefanie Primon Muraro
Support type: Scholarships in Brazil - Doctorate
FAPESP's process: 16/07371-2 - Characterization of the role of T CD8+ lymphocytes in Zika virus infection
Grantee:Nagela Ghabdan Zanluqui
Support type: Scholarships in Brazil - Doctorate