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

Silva-Filho, J. L. et al. (2021) Gas6 drives Zika virus-induced neurological complications in humans and congenital syndrome in immunocompetent mice. Brain, Behavior, and Immunity, 97, pp. 260-274. (doi: 10.1016/j.bbi.2021.08.008) (PMID:34390806)

Full text not currently available from Enlighten.

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.

Item Type:Articles
Status:Published
Refereed:Yes
Glasgow Author(s) Enlighten ID:Da Silva Filho, Dr Joao
Creator Roles:
Silva-Filho, J. L.Conceptualization, Methodology, Investigation
Authors: Silva-Filho, J. L., de Oliveira, L. G., Monteiro, L., Parise, P. L., Zanluqui, N. G., Polonio, C. M., de Freitas, C. L., Toledo-Teixeira, D. A., de Souza, W. M., Bittencourt, N., Amorim, M. R., Forato, J., Muraro, S. P., de Souza, G. F., Martini, M. C., Bispo-dos-Santos, K., Vieira, A., Judice, C. C., Pastore, G. M., Amaral, E., Passini Junior, R., Mayer-Milanez, H. M.B.P., Ribeiro-do-Valle, C. C., Calil, R., Renato Bennini Junior, J., Lajos, G. J., Altemani, A., Nolasco da Silva, M. T., Carolina Coan, A., Francisca Colella-Santos, M., von Zuben, A. P.B., Vinolo, M. A. R., Arns, C. W., Catharino, R. R., Costa, M. L., Angerami, R. N., Freitas, A. R.R., Resende, M. R., Garcia, M. T., Luiza Moretti, M., Renia, L., Ng, L. F.P., Rothlin, C. V., Costa, F. T.M., Peron, J. P. S., and Proença-Modena, J. L.
College/School:College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:Brain, Behavior, and Immunity
Publisher:Elsevier
ISSN:0889-1591
ISSN (Online):1090-2139
Published Online:11 August 2021

University Staff: Request a correction | Enlighten Editors: Update this record