[en] The 2015-2016 Zika virus (ZIKV) outbreak in the Americas revealed the ability of ZIKV from the Asian lineage to cause birth defects, generically called congenital Zika syndrome (CZS). Notwithstanding the long circulation history of Asian ZIKV, no ZIKV-associated CZS cases were reported prior to the outbreaks in French Polynesia (2013) and Brazil (2015). Whether the sudden emergence of CZS resulted from an evolutionary event of Asian ZIKV has remained unclear. We performed a comparative analysis of the pathogenicity of pre-epidemic and epidemic Asian ZIKV strains in mouse embryonic brains using a female immunocompetent intraplacental infection mouse model. All studied Asian ZIKV strains are neurovirulent, but pre-epidemic strains are consistently more pathogenic in the embryos than their epidemic equivalents. Pathogenicity is not directly linked to viral replication. By contrast, an influx of macrophages/microglial cells is noted in infected fetal brains for both pre-epidemic and epidemic ZIKV strains. Moreover, all tested ZIKV strains trigger an immunological response, whereby the intensity of the response differs between strains, and with epidemic ZIKV strains generally mounting a more attenuated immunostimulatory response. Our study reveals that Asian ZIKV strains evolved towards pathogenic attenuation, potentially resulting in CZS emergence in neonates rather than premature death in utero.
Disciplines :
Microbiology
Author, co-author :
Darmuzey, Maïlis ; Virology and Immunology Unit, GIGA-Infection, Immunity and Inflammation, University of Liège, Liège, Belgium ; KU Leuven Department of Microbiology, Immunology and Transplantation, Virology, Antiviral Drug & Vaccine Research Group, Rega Institute for Medical Research, Leuven, Belgium
Touret, Franck ; Unité Des Virus Émergents (UVE: Aix-Marseille University - IRD 190 - Inserm 1207), Marseille, France
Slowikowski, Emily ; KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Molecular Immunology, Rega Institute for Medical Research, Leuven, Belgium
Gladwyn-Ng, Ivan; Department of Application Scientists, Taconic Biosciences, Leverkusen, Germany
Ahuja, Karan; Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium
Sanchez-Felipe, Lorena ; KU Leuven Department of Microbiology, Immunology and Transplantation, Virology, Antiviral Drug & Vaccine Research Group, Rega Institute for Medical Research, Leuven, Belgium
de Lamballerie, Xavier ; Unité Des Virus Émergents (UVE: Aix-Marseille University - IRD 190 - Inserm 1207), Marseille, France
Verfaillie, Catherine ; Department of Development and Regeneration, Stem Cell Institute, KU Leuven, Leuven, Belgium
Marques, Pedro E ; KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Molecular Immunology, Rega Institute for Medical Research, Leuven, Belgium
Neyts, Johan ; KU Leuven Department of Microbiology, Immunology and Transplantation, Virology, Antiviral Drug & Vaccine Research Group, Rega Institute for Medical Research, Leuven, Belgium. johan.neyts@kuleuven.be
Kaptein, Suzanne J F ; KU Leuven Department of Microbiology, Immunology and Transplantation, Virology, Antiviral Drug & Vaccine Research Group, Rega Institute for Medical Research, Leuven, Belgium. suzanne.kaptein@kuleuven.be
Language :
English
Title :
Epidemic Zika virus strains from the Asian lineage induce an attenuated fetal brain pathogenicity.
H2020 - 734584 - ZikaPLAN - Zika Preparedness Latin American Network
Funders :
F.R.S.-FNRS - Fonds de la Recherche Scientifique EU - European Union
Funding text :
We thank Prof. Catherine Sadzot-Delvaux (Li\u00E8ge University, Uli\u00E8ge) for her support. We warmly thank Stijn Hendrickx for technical support. We thank Niels Cremers, Elke Maas, Johanna Bouckaert, Jill Swinnen and the staff at the Rega animal facility at KU Leuven for technical assistance. We thank Jelle Matthijnssens and Lander De Coninck (KU Leuven) for sequencing the ZIKV strains and analyzing the results. We thank Alexandre Hego and the imaging platform at Uli\u00E8ge for their grateful technical help. We thank Martijn van Hemert (LUMC), Alain Kohl (MRC-University of Glasgow Centre for Virus Research), Van-Mai Cao-Lormeau (Institut Louis Malard\u00E9), Richard G. Jarman (WRAIR), and Amadou A. Sall (Institut Pasteur Dakar) for kindly providing the ZIKV strains. This work was primarily funded by the European Union\u2019s Horizon 2020 research and innovation program under ZikaPLAN grant agreement no. 734584 (to J.N.) and under ZIKAlliance grant agreement no. 734548 (to J.N.). This work was also supported by the Fonds de la Recherche Scientifique (FNRS-FRIA Ph.D. fellowship to M.D.). The funders had no role in the\u00A0study design, data collection and interpretation, or the decision to submit the work for publication.We thank Prof. Catherine Sadzot-Delvaux (Li\u00E8ge University, Uli\u00E8ge) for her support. We warmly thank Stijn Hendrickx for technical support. We thank Niels Cremers, Elke Maas, Johanna Bouckaert, Jill Swinnen and the staff at the Rega animal facility at KU Leuven for technical assistance. We thank Jelle Matthijnssens and Lander De Coninck (KU Leuven) for sequencing the ZIKV strains and analyzing the results. We thank Alexandre Hego and the imaging platform at Uli\u00E8ge for their grateful technical help. We thank Martijn van Hemert (LUMC), Alain Kohl (MRC-University of Glasgow Centre for Virus Research), Van-Mai Cao-Lormeau (Institut Louis Malard\u00E9), Richard G. Jarman (WRAIR), and Amadou A. Sall (Institut Pasteur Dakar) for kindly providing the ZIKV strains. This work was primarily funded by the European Union\u2019s Horizon 2020 research and innovation program under ZikaPLAN grant agreement no. 734584 (to J.N.) and under ZIKAlliance grant agreement no. 734548 (to J.N.). This work was also supported by the Fonds de la Recherche Scientifique (FNRS-FRIA Ph.D. fellowship to M.D.). The funders had no role in the study design, data collection and interpretation, or the decision to submit the work for publication.
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