Epidemic Zika virus strains from the Asian lineage induce an attenuated fetal brain pathogenicity
Abstract 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 prio...
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Nature Portfolio
2024-12-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-024-55155-4 |
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| author | Maïlis Darmuzey Franck Touret Emily Slowikowski Ivan Gladwyn-Ng Karan Ahuja Lorena Sanchez-Felipe Xavier de Lamballerie Catherine Verfaillie Pedro E. Marques Johan Neyts Suzanne J. F. Kaptein |
| author_facet | Maïlis Darmuzey Franck Touret Emily Slowikowski Ivan Gladwyn-Ng Karan Ahuja Lorena Sanchez-Felipe Xavier de Lamballerie Catherine Verfaillie Pedro E. Marques Johan Neyts Suzanne J. F. Kaptein |
| author_sort | Maïlis Darmuzey |
| collection | DOAJ |
| description | Abstract 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. |
| format | Article |
| id | doaj-art-cde095291d1f4c02b3c8adeede07f053 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-cde095291d1f4c02b3c8adeede07f0532025-01-05T12:36:22ZengNature PortfolioNature Communications2041-17232024-12-0115111510.1038/s41467-024-55155-4Epidemic Zika virus strains from the Asian lineage induce an attenuated fetal brain pathogenicityMaïlis Darmuzey0Franck Touret1Emily Slowikowski2Ivan Gladwyn-Ng3Karan Ahuja4Lorena Sanchez-Felipe5Xavier de Lamballerie6Catherine Verfaillie7Pedro E. Marques8Johan Neyts9Suzanne J. F. Kaptein10Virology and Immunology Unit, GIGA-Infection, Immunity and Inflammation, University of LiègeUnité Des Virus Émergents (UVE: Aix-Marseille University - IRD 190 - Inserm 1207)KU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Molecular Immunology, Rega Institute for Medical ResearchDepartment of Application Scientists, Taconic BiosciencesDepartment of Development and Regeneration, Stem Cell Institute, KU LeuvenKU Leuven Department of Microbiology, Immunology and Transplantation, Virology, Antiviral Drug & Vaccine Research Group, Rega Institute for Medical ResearchUnité Des Virus Émergents (UVE: Aix-Marseille University - IRD 190 - Inserm 1207)Department of Development and Regeneration, Stem Cell Institute, KU LeuvenKU Leuven Department of Microbiology, Immunology and Transplantation, Laboratory of Molecular Immunology, Rega Institute for Medical ResearchKU Leuven Department of Microbiology, Immunology and Transplantation, Virology, Antiviral Drug & Vaccine Research Group, Rega Institute for Medical ResearchKU Leuven Department of Microbiology, Immunology and Transplantation, Virology, Antiviral Drug & Vaccine Research Group, Rega Institute for Medical ResearchAbstract 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.https://doi.org/10.1038/s41467-024-55155-4 |
| spellingShingle | Maïlis Darmuzey Franck Touret Emily Slowikowski Ivan Gladwyn-Ng Karan Ahuja Lorena Sanchez-Felipe Xavier de Lamballerie Catherine Verfaillie Pedro E. Marques Johan Neyts Suzanne J. F. Kaptein Epidemic Zika virus strains from the Asian lineage induce an attenuated fetal brain pathogenicity Nature Communications |
| title | Epidemic Zika virus strains from the Asian lineage induce an attenuated fetal brain pathogenicity |
| title_full | Epidemic Zika virus strains from the Asian lineage induce an attenuated fetal brain pathogenicity |
| title_fullStr | Epidemic Zika virus strains from the Asian lineage induce an attenuated fetal brain pathogenicity |
| title_full_unstemmed | Epidemic Zika virus strains from the Asian lineage induce an attenuated fetal brain pathogenicity |
| title_short | Epidemic Zika virus strains from the Asian lineage induce an attenuated fetal brain pathogenicity |
| title_sort | epidemic zika virus strains from the asian lineage induce an attenuated fetal brain pathogenicity |
| url | https://doi.org/10.1038/s41467-024-55155-4 |
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