Molecular alterations in the extracellular matrix in the brains of newborns with congenital Zika syndrome
Universidade Federal do Rio de Janeiro (UFRJ)¦¦Brasil ; Universidade Federal de Minas Gerais (UFMG)¦¦Brasil ; (USP) Universidade de São Paulo ; Laboratório Nacional de Computação Científica (LNCC)¦¦Brasil ; Fundação Oswaldo Cruz (Fiocruz)¦¦Brasil ; Instituto Fernandes Figueira (IFF)¦¦Brasil ; Instituto de Pesquisa Professor Joaquim Amorim Neto (IPESQ)¦¦Brasil ; Faculdade de Ciências Médicas de Campina Grande (FCM)¦¦Brasil ; Centro Universitário UNIFACISA¦¦Brasil ; Instituto Estadual do Cérebro Paulo Niemeyer¦¦Brasil
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Zika virus (ZIKV) infection during pregnancy can cause a set of severe abnormalities in the fetus known as congenital Zika syndrome (CZS). Experiments with animal models and in vitro systems have substantially contributed to our understanding of the pathophysiology of ZIKV infection. Here, to investigate the molecular basis of CZS in humans, we used a systems biology approach to integrate transcriptomic, proteomic, and genomic data from the postmortem brains of neonates with CZS. We observed that collagens were greatly reduced in expression in CZS brains at both the RNA and protein levels and that neonates with CZS had several single-nucleotide polymorphisms in collagen-encoding genes that are associated with osteogenesis imperfecta and arthrogryposis. These findings were validated by immunohistochemistry and comparative analysis of collagen abundance in ZIKV-infected and uninfected samples. In addition, we showed a ZIKV-dependent increase in the expression of cell adhesion factors that are essential for neurite outgrowth and axon guidance, findings that are consistent with the neuronal migration defects observed in CZS. Together, these findings provide insights into the underlying molecular alterations in the ZIKV-infected brain and reveal host genes associated with CZS susceptibility.
Aguiar RS., Pohl F, Morais GL., Nogueira FC.S., Carvalho JB., Guida L, et al. Molecular alterations in the extracellular matrix in the brains of newborns with congenital Zika syndrome. Sci. Signal.. 2020 Jun;13(635):eaay6736. doi:10.1126/scisignal.aay6736.
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(CNPq) Conselho Nacional de Desenvolvimento Científico e Tecnológico ; (CAPES) Coordenação de Aperfeiçoamento de Pessoal de Nível Superior ; (FINEP) Financiadora de Estudos e Projetos ; (FAPESP) Fundação de Amparo à Pesquisa do Estado de São Paulo ; (FAPERJ) Fundação de Amparo à Pesquisa do Estado do Rio de Janeiro
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