Brasil | Article

Zika virus NS3 protease induces bone morphogenetic protein-dependent brain calcification in human fetuses

dc.creatorChen, Weiqiang
dc.creatorFoo, Suan-Sin
dc.creatorHong, Eunjin
dc.creatorWu, Christine
dc.creatorLee, Wai-Suet
dc.creatorLee, Shin-Ae
dc.creatorEvseenko, Denis
dc.creatorMoreira, Maria Elisabeth Lopes
dc.creatorGarcía-Sastre, Adolfo
dc.creatorCheng, Genhong
dc.creatorNielsen-Saines, Karin
dc.creatorBrasil, Patrícia
dc.creatorAvvad-Portari, Elyzabeth
dc.creatorJung, Jae U.
dc.date2021-09-22T14:05:55Z
dc.date2021-09-22T14:05:55Z
dc.date2021
dc.date.accessioned2023-09-26T23:17:43Z
dc.date.available2023-09-26T23:17:43Z
dc.identifierCHEN, Weiqiang et al. Zika virus NS3 protease induces bone morphogenetic protein-dependent brain calcification in human fetuses. Nature Microbiology, v. 6, p. 455-466, 28 Jan. 2021.
dc.identifier2058-5276
dc.identifierhttps://www.arca.fiocruz.br/handle/icict/49131
dc.identifier10.1038/s41564-020-00850-3
dc.identifier2058-5276
dc.identifier.urihttps://repositorioslatinoamericanos.uchile.cl/handle/2250/8888990
dc.descriptionDr. Jae U. Jung is a scientific adviser of the Vaccine Stabilization, a California corporation
dc.descriptionR01 AR071734/AR/NIAMS NIH HHS/United States
dc.descriptionR01 AI116585/AI/NIAID NIH HHS/United States
dc.descriptionR21 DE027888/DE/NIDCR NIH HHS/United States
dc.descriptionR01 AI069120/AI/NIAID NIH HHS/United States
dc.descriptionR01 AI140718/AI/NIAID NIH HHS/United States
dc.descriptionThe 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.
dc.formatapplication/pdf
dc.languageeng
dc.publisherNature Research
dc.rightsrestricted access
dc.subjectAnimals
dc.subjectBone Morphogenetic Protein 2 / metabolism
dc.subjectBone Morphogenetic Proteins / metabolism
dc.subjectBrain / metabolism
dc.subjectBrain / pathology
dc.subjectBrain / virology
dc.subjectCalcinosis / metabolism
dc.subjectCalcinosis / pathology
dc.subjectCalcinosis / virology
dc.subjectCalcium / metabolism
dc.subjectCells, Cultured
dc.subjectFetus / pathology
dc.subjectFetus / virology
dc.subjectHumans
dc.subjectInfectious Disease Transmission, Vertical
dc.subjectMice
dc.subjectMice, Transgenic
dc.subjectOsteogenesis / genetics
dc.subjectPericytes
dc.subjectSTAT2 Transcription Factor / genetics
dc.subjectSTAT2 Transcription Factor / metabolism
dc.subjectSerine Endopeptidases / metabolism
dc.subjectSignal Transduction Viral Proteins / metabolism
dc.subjectZika Virus / enzymology
dc.subjectZika Virus / pathogenicity
dc.subjectZika Virus Infection / metabolism
dc.subjectZika Virus Infection / pathology
dc.subjectZika Virus Infection / virology
dc.subjectZika Virus Infection / transmission
dc.subjectZika Virus
dc.subjectFlaviviruses
dc.subjectFetal brain calcification
dc.subjectBMP2
dc.subjectOsteogenic signaling
dc.subjectNS3 protease
dc.titleZika virus NS3 protease induces bone morphogenetic protein-dependent brain calcification in human fetuses
dc.typeArticle


Este ítem pertenece a la siguiente institución