EBioMedicine (Jun 2019)
In-depth characterization of congenital Zika syndrome in immunocompetent mice: Antibody-dependent enhancement and an antiviral peptide therapyResearch in context
- Vidyleison N. Camargos,
- Giselle Foureaux,
- Daniel C. Medeiros,
- Vivian T. da Silveira,
- Celso M. Queiroz-Junior,
- Ana Luisa B. Matosinhos,
- André F.A. Figueiredo,
- Carla D.F. Sousa,
- Thaiane P. Moreira,
- Victória F. Queiroz,
- Ana Carolina F. Dias,
- Karina T.O. Santana,
- Ingredy Passos,
- Ana Luíza C.V. Real,
- Ludmila C. Silva,
- Flávio A.G. Mourão,
- Natália T. Wnuk,
- Milton A.P. Oliveira,
- Soraia Macari,
- Tarcília Silva,
- Gustavo P. Garlet,
- Joshua A. Jackman,
- Frederico M. Soriani,
- Márcio F.D. Moraes,
- Eduardo M.A.M. Mendes,
- Fabíola M. Ribeiro,
- Guilherme M.J. Costa,
- Antônio L. Teixeira,
- Nam-Joon Cho,
- Antônio C.P. Oliveira,
- Mauro M. Teixeira,
- Vivian V. Costa,
- Danielle G. Souza
Affiliations
- Vidyleison N. Camargos
- Host-Microorganism Interaction Lab, Department of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- Giselle Foureaux
- Transversal Biology Lab, Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- Daniel C. Medeiros
- Centre for Technology and Research in Magnetic-Resonance, Graduate Program in Electrical Engineering, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- Vivian T. da Silveira
- Neuropharmacology Lab, Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- Celso M. Queiroz-Junior
- Transversal Biology Lab, Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- Ana Luisa B. Matosinhos
- Neuropharmacology Lab, Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- André F.A. Figueiredo
- Cellular Biology Lab, Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- Carla D.F. Sousa
- Host-Microorganism Interaction Lab, Department of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- Thaiane P. Moreira
- Host-Microorganism Interaction Lab, Department of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- Victória F. Queiroz
- Host-Microorganism Interaction Lab, Department of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- Ana Carolina F. Dias
- Host-Microorganism Interaction Lab, Department of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- Karina T.O. Santana
- Centre for Drug Research and Development of Pharmaceuticals, Institute of Biological Sciences, Universidade Federal de Minas Gerais, MG, Brazil
- Ingredy Passos
- Centre for Drug Research and Development of Pharmaceuticals, Institute of Biological Sciences, Universidade Federal de Minas Gerais, MG, Brazil; Research Group in Arboviral Diseases, Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, MG, Brazil
- Ana Luíza C.V. Real
- Neurobiochemistry Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- Ludmila C. Silva
- Transversal Biology Lab, Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- Flávio A.G. Mourão
- Centre for Technology and Research in Magnetic-Resonance, Graduate Program in Electrical Engineering, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- Natália T. Wnuk
- Cellular Biology Lab, Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- Milton A.P. Oliveira
- Department of Microbiology, Immunology, Parasitology and Pathology, Tropical Pathology and Public Health Institute, Federal University of Goiás, Goiania, GO, Brazil
- Soraia Macari
- Department of Paediatric Dentistry and Orthodontics, Faculty of Dentistry, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil
- Tarcília Silva
- Department of Oral Pathology and Surgery, Faculty of Dentistry, Federal University of Minas Gerais, Belo Horizonte, MG, Brazil
- Gustavo P. Garlet
- Department of Biological Sciences, School of Dentistry of Bauru, São Paulo University, Bauru, SP, Brazil
- Joshua A. Jackman
- School of Materials Science and Engineering, Nanyang Technological University, Singapore
- Frederico M. Soriani
- Centre for Drug Research and Development of Pharmaceuticals, Institute of Biological Sciences, Universidade Federal de Minas Gerais, MG, Brazil
- Márcio F.D. Moraes
- Centre for Technology and Research in Magnetic-Resonance, Graduate Program in Electrical Engineering, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- Eduardo M.A.M. Mendes
- Centre for Technology and Research in Magnetic-Resonance, Graduate Program in Electrical Engineering, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- Fabíola M. Ribeiro
- Neurobiochemistry Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- Guilherme M.J. Costa
- Cellular Biology Lab, Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- Antônio L. Teixeira
- Neuropsychiatry Program, Department of Psychiatry and Behavioural Sciences, McGovern Medical Houston, University of Texas Health Science Center at Houston, Houston, TX, USA
- Nam-Joon Cho
- School of Materials Science and Engineering, Nanyang Technological University, Singapore
- Antônio C.P. Oliveira
- Neuropharmacology Lab, Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil
- Mauro M. Teixeira
- Immunopharmacology Lab, Department of Biochemistry and Immunology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, MG, Brazil; Centre for Drug Research and Development of Pharmaceuticals, Institute of Biological Sciences, Universidade Federal de Minas Gerais, MG, Brazil
- Vivian V. Costa
- Centre for Drug Research and Development of Pharmaceuticals, Institute of Biological Sciences, Universidade Federal de Minas Gerais, MG, Brazil; Research Group in Arboviral Diseases, Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, MG, Brazil; Corresponding authorst at: Departamento de Morfologia and Departamento de Microbiologia, respectively. Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha, CEP 31270-901, Belo Horizonte, MG, Brasil.
- Danielle G. Souza
- Host-Microorganism Interaction Lab, Department of Microbiology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, MG, Brazil; Corresponding authorst at: Departamento de Morfologia and Departamento de Microbiologia, respectively. Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Avenida Antônio Carlos, 6627, Pampulha, CEP 31270-901, Belo Horizonte, MG, Brasil.
- Journal volume & issue
-
Vol. 44
pp. 516 – 529
Abstract
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. Fund: This work was supported by the Brazilian National Science Council (CNPq, Brazil), Minas Gerais Foundation for Science (FAPEMIG), Funding Authority for Studies and Projects (FINEP), Coordination of Superior Level Staff Improvement (CAPES), National Research Foundation of Singapore and Centre for Precision Biology at Nanyang Technological University. Keywords: Congenital Zika virus infection (CZI), Congenital Zika Syndrome (CZS), Maternal immune activation (MIA), Antibody-dependent enhancement (ADE), Short and long-term outcomes
