Molecular alterations in the extracellular matrix in the brains of newborns with congenital Zika syndrome

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Aguiar, Renato S. ; Pohl, Fabio ; Morais, Guilherme L. ; Nogueira, Fabio C. S. ; de Carvalho, Joseane B. ; Guida, Leticia ; Arge, Luis W. P. ; Melo, Adriana ; Moreira, Maria E. L. ; Cunha, Daniela P. ; Gomes, Leonardo ; Portari, Elyzabeth A. ; Velasquez, Erika ; Melani, Rafael D. ; Pezzuto, Paula ; de Castro, Fernanda L. ; Geddes, Victor E. V. ; Gerber, Alexandra L. ; Azevedo, Girlene S. ; Schamber-Reis, Bruno L. ; Goncalves, Alessandro L. ; Junqueira-de-Azevedo, Inacio ; Nishiyama Jr, Milton Y. ; Ho, Paulo ; Schanoski, Alessandra ; Schuch, Viviane ; Tanuri, Amilcar ; Chimelli, Leila ; Vasconcelos, Zilton F. M. ; Domont, Gilberto B. ; Vasconcelos, Ana T. R. ; Nakaya, Helder, I

• Tipo de documento: Artigo Científico
• Fonte: SCIENCE SIGNALING; v. 13, n. 635, p. 13-pg., 2020-06-09.

Resumo

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. (AU)

• Processo FAPESP: 13/08216-2 - CPDI - Centro de Pesquisa em Doenças Inflamatórias
• Beneficiário: Fernando de Queiroz Cunha
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 17/50137-3 - Long noncoding RNA interplay with the host microbiome may determine mucosal influenza vaccine immunogenicity
• Beneficiário: Helder Takashi Imoto Nakaya
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 18/14933-2 - Biologia integrativa aplicada à saúde humana
• Beneficiário: Helder Takashi Imoto Nakaya
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores - Fase 2
• Processo FAPESP: 18/21934-5 - Estatística de redes: teoria, métodos e aplicações
• Beneficiário: André Fujita
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 12/19278-6 - Biologia de sistemas de longos RNAs não-codificadores
• Beneficiário: Helder Takashi Imoto Nakaya
• Modalidade de apoio: Auxílio à Pesquisa - Jovens Pesquisadores