Discordant congenital Zika syndrome twins show differential in vitro viral susceptibility of neural progenitor cells

Author(s):Show less -

de Caires, Jr., Luiz Carlos ^[1] ; Goulart, Ernesto ^[1] ; Melo, UiraSouto ^[1] ; Henrique Araujo, Bruno Silva ^{[2, 3]} ; Alvizi, Lucas ^[1] ; Schanoski, Alessandra Soares ^[4] ; de Oliveira, Danyllo Felipe ^[1] ; Kobayashi, Gerson Shigeru ^[1] ; Griesi-Oliveira, Karina ^{[1, 5]} ; Musso, Camila Manso ^[1] ; Amaral, MuriloSena ^[4] ; dasilva, Lucas Ferreira ^[6] ; Astray, Renato Mancini ^[4] ; Suarez-Patino, Sandra Fernanda ^[4] ; Ventini, Daniella Cristina ^[4] ; da Silva, Sergio Gomes ^{[7, 5]} ; Yamamoto, Guilherme Lopes ^[1] ; Ezquina, Suzana ^[1] ; Naslavsky, Michel Satya ^[1] ; Alves Silva, Kayque Telles ^[1] ; Weinmann, Karina ^[1] ; Van der Linden, Vanessa ^[8] ; Van der Linden, Helio ^[9] ; Ricardo de Oliveira, Joao Mendes ^{[10, 11]} ; Maria Arrais, Nivia Rodrigues ^[12] ; Melo, Adriana ^[13] ; Figueiredo, Thalita ^{[14, 1]} ; Santos, Silvana ; Goes Meira, Joanna Castro ^[15] ; Passos, Saulo Duarte ^[16] ; de Almeida, Roque Pacheco ^{[17, 18]} ; Bispo, Ana JovinaBarreto ^{[17, 18]} ; Cavalheiro, EsperAbrao ^[3] ; Kalil, Jorge ^[4] ; Cunha-Neto, Edecio ^[19] ; Nakaya, Helder ^[20] ; Santos, Robert Andreata ^[21] ; de Souza Ferreira, Luis Carlos ^[21] ; Verjovski-Almeida, Sergio ^{[4, 6]} ; Ho, Paulo Lee ^[4] ; Passos-Bueno, Maria Rita ^[1] ; Zatz, Mayana ^[1]

Affiliation:Show less -

^[1] Univ Sao Paulo, Biosci Inst, Human Genome & Stem Cell Res Ctr, Dept Genet & Evolutionary Biol, BR-05508900 Sao Paulo, SP - Brazil

^[2] Brazilian Ctr Res Energy & Mat CNPEM, Brazilian Biosci Natl Lab LNBio, BR-13083970 Campinas, SP - Brazil

^[3] Fed Univ Sao Paulo Univ UNIFESP EPM, Dept Neurol & Neurosurg, Neurosci Lab, BR-04039002 Sao Paulo, SP - Brazil

^[4] Butantan Inst, BR-05503900 Sao Paulo, SP - Brazil

^[5] Albert Einstein Hosp, BR-05652900 Sao Paulo, SP - Brazil

^[6] Univ Sao Paulo, Inst Chem, Dept Biochem, BR-05508900 Sao Paulo, SP - Brazil

^[7] Univ Mogi das Cruzes, BR-08780911 Mogi Das Cruzes, SP - Brazil

^[8] AACD, BR-50080810 Recife, PE - Brazil

^[9] Rehabil Ctr Dr Henrique Santillo, BR-74653230 Goiania, Go - Brazil

^[10] Fed Univ Pernambuco UFPE, Neuropsychiat Dept, BR-50670901 Recife, PE - Brazil

^[11] Fed Univ Pernambuco UFPE, KeizoAsami Lab, BR-50670901 Recife, PE - Brazil

^[12] Fed Univ Rio Grande Norte UFRN, Dept Pediat, BR-59010180 Natal, RN - Brazil

^[13] ISEA, BR-58400220 Campina Grande, PB - Brazil

^[14] Paraiba State Univ UEPB, Dept Biol, BR-58429500 Campina Grande, PB - Brazil

^[15] Fed Univ Bahia UFBA, BR-40170115 Salvador, BA - Brazil

^[16] Med Sch Jundiai, Infect Pediat Lab, BR-13202550 Jundiai, SP - Brazil

^[17] Fed Univ Sergipe UFS, Div Immunol, BR-49100000 Aracaju, SP - Brazil

^[18] Fed Univ Sergipe UFS, Mol Biol Lab, BR-49100000 Aracaju, SP - Brazil

^[19] Univ Sao Paulo, Fac Med, Heart Inst, BR-05403900 Sao Paulo, SP - Brazil

^[20] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, BR-05508900 Sao Paulo, SP - Brazil

^[21] Univ Sao Paulo, Inst Biomed Sci, Dept Microbiol, Vaccine Dev Lab, BR-05508900 Sao Paulo, SP - Brazil

• Document type: Journal article
• Source: NATURE COMMUNICATIONS; v. 9, FEB 2 2018.
• Web of Science Citations: 9

Abstract

Congenital Zika syndrome (CZS) causes early brain development impairment by affecting neural progenitor cells (NPCs). Here, we analyze NPCs from three pairs of dizygotic twins discordant for CZS. We compare by RNA-Seq the NPCs derived from CZS-affected and CZS-unaffected twins. Prior to Zika virus (ZIKV) infection the NPCs from CZS babies show a significantly different gene expression signature of mTOR and Wnt pathway regulators, key to a neurodevelopmental program. Following ZIKV in vitro infection, cells from affected individuals have significantly higher ZIKV replication and reduced cell growth. Whole-exome analysis in 18 affected CZS babies as compared to 5 unaffected twins and 609 controls excludes a monogenic model to explain resistance or increased susceptibility to CZS development. Overall, our results indicate that CZS is not a stochastic event and depends on NPC intrinsic susceptibility, possibly related to oligogenic and/or epigenetic mechanisms. (AU)

• FAPESP's process: 14/50931-3 - Aging and genetic disorders: genomics and metagenomics
• Grantee: Mayana Zatz
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 14/03620-2 - Characterization of the mechanisms of action of long non-coding RNAs involved with gene activation programs in human cells
• Grantee: Sergio Verjovski Almeida
• Support Opportunities: Research Projects - Thematic Grants
• FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
• Grantee: Mayana Zatz
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC