| Author | Chen, Weiqiang | pt_BR |
| Author | Foo, Suan-Sin | pt_BR |
| Author | Hong, Eunjin | pt_BR |
| Author | Wu, Christine | pt_BR |
| Author | Lee, Wai-Suet | pt_BR |
| Author | Lee, Shin-Ae | pt_BR |
| Author | Evseenko, Denis | pt_BR |
| Author | Moreira, Maria Elisabeth Lopes | pt_BR |
| Author | García-Sastre, Adolfo | pt_BR |
| Author | Cheng, Genhong | pt_BR |
| Author | Nielsen-Saines, Karin | pt_BR |
| Author | Brasil, Patrícia | pt_BR |
| Author | Avvad-Portari, Elyzabeth | pt_BR |
| Author | Jung, Jae U. | pt_BR |
| Access date | 2021-09-22T14:05:55Z | |
| Available date | 2021-09-22T14:05:55Z | |
| Document date | 2021 | |
| Citation | CHEN, Weiqiang et al. Zika virus NS3 protease induces bone morphogenetic protein-dependent brain calcification in human fetuses. Nature Microbiology, v. 6, p. 455-466, Jan. 2021. | pt_BR |
| ISSN | 2058-5276 | pt_BR |
| URI | https://www.arca.fiocruz.br/handle/icict/49131 | |
| Sponsorship | R01 AR071734/AR/NIAMS NIH HHS/United States | pt_BR |
| Sponsorship | R01 AI116585/AI/NIAID NIH HHS/United States | pt_BR |
| Sponsorship | R21 DE027888/DE/NIDCR NIH HHS/United States | pt_BR |
| Sponsorship | R01 AI069120/AI/NIAID NIH HHS/United States | pt_BR |
| Sponsorship | R01 AI140718/AI/NIAID NIH HHS/United States | pt_BR |
| Language | eng | pt_BR |
| Publisher | Nature Research | pt_BR |
| Rights | open access | |
| MeSH | Animals | pt_BR |
| MeSH | Bone Morphogenetic Protein 2 / metabolism | pt_BR |
| MeSH | Bone Morphogenetic Proteins / metabolism | pt_BR |
| MeSH | Brain / metabolism | pt_BR |
| MeSH | Brain / pathology | pt_BR |
| MeSH | Brain / virology | pt_BR |
| MeSH | Calcinosis / metabolism | pt_BR |
| MeSH | Calcinosis / pathology | pt_BR |
| MeSH | Calcinosis / virology | pt_BR |
| MeSH | Calcium / metabolism | pt_BR |
| MeSH | Cells, Cultured | pt_BR |
| MeSH | Fetus / pathology | pt_BR |
| MeSH | Fetus / virology | pt_BR |
| MeSH | Humans | pt_BR |
| MeSH | Infectious Disease Transmission, Vertical | pt_BR |
| MeSH | Mice | pt_BR |
| MeSH | Mice, Transgenic | pt_BR |
| MeSH | Osteogenesis / genetics | pt_BR |
| MeSH | Pericytes | pt_BR |
| MeSH | STAT2 Transcription Factor / genetics | pt_BR |
| MeSH | STAT2 Transcription Factor / metabolism | pt_BR |
| MeSH | Serine Endopeptidases / metabolism | pt_BR |
| MeSH | Signal Transduction Viral Proteins / metabolism | pt_BR |
| MeSH | Zika Virus / enzymology | pt_BR |
| MeSH | Zika Virus / pathogenicity | pt_BR |
| MeSH | Zika Virus Infection / metabolism | pt_BR |
| MeSH | Zika Virus Infection / pathology | pt_BR |
| MeSH | Zika Virus Infection / virology | pt_BR |
| MeSH | Zika Virus Infection / transmission | pt_BR |
| Title | Zika virus NS3 protease induces bone morphogenetic protein-dependent brain calcification in human fetuses | en |
| Type | Article | pt_BR |
| DOI | 10.1038/s41564-020-00850-3 | pt_BR |
| Abstract | The most frequent fetal birth defect associated with prenatal Zika virus (ZIKV) infection is brain calcification, which in turn may potentially affect neurological development in infants. Understanding the mechanism could inform the development of potential therapies against prenatal ZIKV brain calcification. In perivascular cells, bone morphogenetic protein (BMP) is an osteogenic factor that undergoes maturation to activate osteogenesis and calcification. Here, we show that ZIKV infection of cultivated primary human brain pericytes triggers BMP2 maturation, leading to osteogenic gene expression and calcification. We observed extensive calcification near ZIKV+ pericytes of fetal human brain specimens and in vertically transmitted ZIKV+ human signal transducer and activator of transcription 2-knockin mouse pup brains. ZIKV infection of primary pericytes stimulated BMP2 maturation, inducing osteogenic gene expression and calcification that were completely blocked by anti-BMP2/4 neutralizing antibody. Not only did ZIKV NS3 expression alone induce BMP2 maturation, osteogenic gene expression and calcification, but purified NS3 protease also effectively cleaved pro-BMP2 in vitro to generate biologically active mature BMP2. These findings highlight ZIKV-induced calcification where the NS3 protease subverts the BMP2-mediated osteogenic signalling pathway to trigger brain calcification. | en |
| Affilliation | Lerner Research Institute. Department of Cancer Biology and Global Center for Pathogens Research and Human Health. Cleveland Clinic. Cleveland, OH, USA. | pt_BR |
| Affilliation | Lerner Research Institute. Department of Cancer Biology and Global Center for Pathogens Research and Human Health. Cleveland Clinic. Cleveland, OH, USA. | pt_BR |
| Affilliation | University of Southern California. Keck School of Medicine. Los Angeles, CA, USA. | pt_BR |
| Affilliation | University of Southern California. Keck School of Medicine. Los Angeles, CA, USA. | pt_BR |
| Affilliation | University of Southern California. Keck School of Medicine. Los Angeles, CA, USA. | pt_BR |
| Affilliation | Lerner Research Institute. Department of Cancer Biology and Global Center for Pathogens Research and Human Health. Cleveland Clinic. Cleveland, OH, USA. | pt_BR |
| Affilliation | University of Southern California. Keck School of Medicine. Los Angeles, CA, USA. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Icahn School of Medicine at Mount Sinai. Department of Microbiology. New York, NY, USA / Icahn School of Medicine at Mount Sinai. Division of Infectious Diseases. Department of Medicine. New York, NY, USA / Icahn School of Medicine at Mount Sinai. Global Health and Emerging Pathogens Institute. New York, NY, USA / Icahn School of Medicine at Mount Sinai. The Tisch Cancer Institute. New York, NY, USA. | pt_BR |
| Affilliation | University of California. David Geffen School of Medicine. Department of Microbiology and Molecular Genetics. Los Angeles, CA, USA. | pt_BR |
| Affilliation | University of California. David Geffen School of Medicine. Division of Pediatric Infectious Diseases. Los Angeles, CA, USA. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Infectologia Evandro Chagas. Laboratório de Pesquisa Clínica em Doenças Febris Agudas. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Fundação Oswaldo Cruz. Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira. Departamento de Patologia. Rio de Janeiro, RJ, Brasil. | pt_BR |
| Affilliation | Lerner Research Institute. Department of Cancer Biology and Global Center for Pathogens Research and Human Health. Cleveland Clinic. Cleveland, OH, USA. | pt_BR |
| Subject | Zika Virus | en |
| Subject | Flaviviruses | en |
| Subject | Fetal brain calcification | en |
| Subject | BMP2 | en |
| Subject | Osteogenic signaling | en |
| Subject | NS3 protease | en |
| e-ISSN | 2058-5276 | pt_BR |
