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

Author(s):Show less -

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

• Document type: Journal article
• Source: SCIENCE SIGNALING; v. 13, n. 635, p. 13-pg., 2020-06-09.

Abstract

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)

• FAPESP's process: 13/08216-2 - CRID - Center for Research in Inflammatory Diseases
• Grantee: Fernando de Queiroz Cunha
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC
• FAPESP's process: 17/50137-3 - Long noncoding RNA interplay with the host microbiome may determine mucosal influenza vaccine immunogenicity
• Grantee: Helder Takashi Imoto Nakaya
• Support Opportunities: Regular Research Grants
• FAPESP's process: 18/14933-2 - Integrative biology applied to human health
• Grantee: Helder Takashi Imoto Nakaya
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2
• FAPESP's process: 18/21934-5 - Network statistics: theory, methods, and applications
• Grantee: André Fujita
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 12/19278-6 - Systems biology of long non-coding RNAs
• Grantee: Helder Takashi Imoto Nakaya
• Support Opportunities: Research Grants - Young Investigators Grants