In-depth characterization of congenital Zika syndrome in immunocompetent mice : antibody-dependent enhancement and an antiviral peptide therapy

Background: Zika virus (ZIKV) infection during pregnancy may cause major congenital defects, including microcephaly, ocular, articular and muscle abnormalities, which are collectively defined as Congenital Zika Syndrome. Here, we performed an in-depth characterization of the effects of congenital ZI...

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Main Authors: Camargos, Vidyleison N., Foureaux, Giselle, Medeiros, Daniel C., da Silveira, Vivian T., Queiroz-Junior, Celso M., Matosinhos, Ana Luisa B., Moreira, Thaiane P., Queiroz, Victória F., Dias, Ana Carolina F., Passos, Ingredy, Silva, Ludmila C., Wnuk, Natália T., Macari, Soraia, Silva, Tarcília, Garlet, Gustavo P., Jackman, Joshua A., Soriani, Frederico M., Ribeiro, Fabíola M., Teixeira, Antônio L., Cho, Nam-Joon, Teixeira, Mauro M., Costa, Vivian V., Souza, Danielle G., Figueiredo, André F. A., Sousa, Carla D. F., Santana, Karina T. O., Real, Ana Luíza C. V., Mourão, Flávio A. G., Oliveira, Milton A. P., Moraes, Márcio F. D., Mendes, Eduardo M. A. M., Costa, Guilherme M. J., Oliveira, Antônio C. P.
Other Authors: School of Materials Science & Engineering
Format: Journal Article
Language:English
Published: 2019
Subjects:
Online Access:https://hdl.handle.net/10356/88024
http://hdl.handle.net/10220/49309
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author Camargos, Vidyleison N.
Foureaux, Giselle
Medeiros, Daniel C.
da Silveira, Vivian T.
Queiroz-Junior, Celso M.
Matosinhos, Ana Luisa B.
Moreira, Thaiane P.
Queiroz, Victória F.
Dias, Ana Carolina F.
Passos, Ingredy
Silva, Ludmila C.
Wnuk, Natália T.
Macari, Soraia
Silva, Tarcília
Garlet, Gustavo P.
Jackman, Joshua A.
Soriani, Frederico M.
Ribeiro, Fabíola M.
Teixeira, Antônio L.
Cho, Nam-Joon
Teixeira, Mauro M.
Costa, Vivian V.
Souza, Danielle G.
Figueiredo, André F. A.
Sousa, Carla D. F.
Santana, Karina T. O.
Real, Ana Luíza C. V.
Mourão, Flávio A. G.
Oliveira, Milton A. P.
Moraes, Márcio F. D.
Mendes, Eduardo M. A. M.
Costa, Guilherme M. J.
Oliveira, Antônio C. P.
author2 School of Materials Science & Engineering
author_facet School of Materials Science & Engineering
Camargos, Vidyleison N.
Foureaux, Giselle
Medeiros, Daniel C.
da Silveira, Vivian T.
Queiroz-Junior, Celso M.
Matosinhos, Ana Luisa B.
Moreira, Thaiane P.
Queiroz, Victória F.
Dias, Ana Carolina F.
Passos, Ingredy
Silva, Ludmila C.
Wnuk, Natália T.
Macari, Soraia
Silva, Tarcília
Garlet, Gustavo P.
Jackman, Joshua A.
Soriani, Frederico M.
Ribeiro, Fabíola M.
Teixeira, Antônio L.
Cho, Nam-Joon
Teixeira, Mauro M.
Costa, Vivian V.
Souza, Danielle G.
Figueiredo, André F. A.
Sousa, Carla D. F.
Santana, Karina T. O.
Real, Ana Luíza C. V.
Mourão, Flávio A. G.
Oliveira, Milton A. P.
Moraes, Márcio F. D.
Mendes, Eduardo M. A. M.
Costa, Guilherme M. J.
Oliveira, Antônio C. P.
author_sort Camargos, Vidyleison N.
collection NTU
description Background: Zika virus (ZIKV) infection during pregnancy may cause major congenital defects, including microcephaly, ocular, articular and muscle abnormalities, which are collectively defined as Congenital Zika Syndrome. Here, we performed an in-depth characterization of the effects of congenital ZIKV infection (CZI) in immunocompetent mice. Methods: Pregnant dams were inoculated with ZIKV on embryonic day 5.5 in the presence or absence of a sub-neutralizing dose of a pan-flavivirus monoclonal antibody (4G2) to evaluate the potential role of antibody-dependent enhancement phenomenon (ADE) during short and long outcomes of CZI. Findings: ZIKV infection induced maternal immune activation (MIA), which was associated with occurrence of foetal abnormalities and death. Therapeutic administration of AH-D antiviral peptide during the early stages of pregnancy prevented ZIKV replication and death of offspring. In the post-natal period, CZI was associated with a decrease in whole brain volume, ophthalmologic abnormalities, changes in testicular morphology, and disruption in bone microarchitecture. Some alterations were enhanced in the presence of 4G2 antibody. Interpretation: Our results reveal that early maternal ZIKV infection causes several birth defects in immunocompetent mice, which can be potentiated by ADE phenomenon and are associated with MIA. Additionally, antiviral treatment with AH-D peptide may be beneficial during early maternal ZIKV infection.
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spelling ntu-10356/880242023-07-14T15:50:22Z In-depth characterization of congenital Zika syndrome in immunocompetent mice : antibody-dependent enhancement and an antiviral peptide therapy Camargos, Vidyleison N. Foureaux, Giselle Medeiros, Daniel C. da Silveira, Vivian T. Queiroz-Junior, Celso M. Matosinhos, Ana Luisa B. Moreira, Thaiane P. Queiroz, Victória F. Dias, Ana Carolina F. Passos, Ingredy Silva, Ludmila C. Wnuk, Natália T. Macari, Soraia Silva, Tarcília Garlet, Gustavo P. Jackman, Joshua A. Soriani, Frederico M. Ribeiro, Fabíola M. Teixeira, Antônio L. Cho, Nam-Joon Teixeira, Mauro M. Costa, Vivian V. Souza, Danielle G. Figueiredo, André F. A. Sousa, Carla D. F. Santana, Karina T. O. Real, Ana Luíza C. V. Mourão, Flávio A. G. Oliveira, Milton A. P. Moraes, Márcio F. D. Mendes, Eduardo M. A. M. Costa, Guilherme M. J. Oliveira, Antônio C. P. School of Materials Science & Engineering Congenital Zika Virus Infection Congenital Zika Syndrome Engineering::Materials Background: Zika virus (ZIKV) infection during pregnancy may cause major congenital defects, including microcephaly, ocular, articular and muscle abnormalities, which are collectively defined as Congenital Zika Syndrome. Here, we performed an in-depth characterization of the effects of congenital ZIKV infection (CZI) in immunocompetent mice. Methods: Pregnant dams were inoculated with ZIKV on embryonic day 5.5 in the presence or absence of a sub-neutralizing dose of a pan-flavivirus monoclonal antibody (4G2) to evaluate the potential role of antibody-dependent enhancement phenomenon (ADE) during short and long outcomes of CZI. Findings: ZIKV infection induced maternal immune activation (MIA), which was associated with occurrence of foetal abnormalities and death. Therapeutic administration of AH-D antiviral peptide during the early stages of pregnancy prevented ZIKV replication and death of offspring. In the post-natal period, CZI was associated with a decrease in whole brain volume, ophthalmologic abnormalities, changes in testicular morphology, and disruption in bone microarchitecture. Some alterations were enhanced in the presence of 4G2 antibody. Interpretation: Our results reveal that early maternal ZIKV infection causes several birth defects in immunocompetent mice, which can be potentiated by ADE phenomenon and are associated with MIA. Additionally, antiviral treatment with AH-D peptide may be beneficial during early maternal ZIKV infection. NRF (Natl Research Foundation, S’pore) Published version 2019-07-12T01:26:22Z 2019-12-06T16:54:21Z 2019-07-12T01:26:22Z 2019-12-06T16:54:21Z 2019 Journal Article Camargos, V. N., Foureaux, G., Medeiros, D. C., da Silveira, V. T., Queiroz-Junior, C. M., Matosinhos, A. L. B., . . . Souza, D. G. (2019). In-depth characterization of congenital Zika syndrome in immunocompetent mice : antibody-dependent enhancement and an antiviral peptide therapy. EBioMedicine, 44, 516-529. doi:10.1016/j.ebiom.2019.05.014 https://hdl.handle.net/10356/88024 http://hdl.handle.net/10220/49309 10.1016/j.ebiom.2019.05.014 en EBioMedicine © 2019 The Author(s). Published by Elsevier B.V. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). 14 p. application/pdf
spellingShingle Congenital Zika Virus Infection
Congenital Zika Syndrome
Engineering::Materials
Camargos, Vidyleison N.
Foureaux, Giselle
Medeiros, Daniel C.
da Silveira, Vivian T.
Queiroz-Junior, Celso M.
Matosinhos, Ana Luisa B.
Moreira, Thaiane P.
Queiroz, Victória F.
Dias, Ana Carolina F.
Passos, Ingredy
Silva, Ludmila C.
Wnuk, Natália T.
Macari, Soraia
Silva, Tarcília
Garlet, Gustavo P.
Jackman, Joshua A.
Soriani, Frederico M.
Ribeiro, Fabíola M.
Teixeira, Antônio L.
Cho, Nam-Joon
Teixeira, Mauro M.
Costa, Vivian V.
Souza, Danielle G.
Figueiredo, André F. A.
Sousa, Carla D. F.
Santana, Karina T. O.
Real, Ana Luíza C. V.
Mourão, Flávio A. G.
Oliveira, Milton A. P.
Moraes, Márcio F. D.
Mendes, Eduardo M. A. M.
Costa, Guilherme M. J.
Oliveira, Antônio C. P.
In-depth characterization of congenital Zika syndrome in immunocompetent mice : antibody-dependent enhancement and an antiviral peptide therapy
title In-depth characterization of congenital Zika syndrome in immunocompetent mice : antibody-dependent enhancement and an antiviral peptide therapy
title_full In-depth characterization of congenital Zika syndrome in immunocompetent mice : antibody-dependent enhancement and an antiviral peptide therapy
title_fullStr In-depth characterization of congenital Zika syndrome in immunocompetent mice : antibody-dependent enhancement and an antiviral peptide therapy
title_full_unstemmed In-depth characterization of congenital Zika syndrome in immunocompetent mice : antibody-dependent enhancement and an antiviral peptide therapy
title_short In-depth characterization of congenital Zika syndrome in immunocompetent mice : antibody-dependent enhancement and an antiviral peptide therapy
title_sort in depth characterization of congenital zika syndrome in immunocompetent mice antibody dependent enhancement and an antiviral peptide therapy
topic Congenital Zika Virus Infection
Congenital Zika Syndrome
Engineering::Materials
url https://hdl.handle.net/10356/88024
http://hdl.handle.net/10220/49309
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