DataSheet_1_Congenital Zika Syndrome Is Associated With Interferon Alfa Receptor 1.docx (1.32 MB)

DataSheet_1_Congenital Zika Syndrome Is Associated With Interferon Alfa Receptor 1.docx

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posted on 2021-11-25, 12:37 authored by Tamiris Azamor, Daniela Prado Cunha, Andréa Marques Vieira da Silva, Ohanna Cavalcanti de Lima Bezerra, Marcelo Ribeiro-Alves, Thyago Leal Calvo, Fernanda de Souza Gomes Kehdy, Fernanda Saloum de Neves Manta, Thiago Gomes de Toledo Pinto, Laís Pereira Ferreira, Elyzabeth Avvad Portari, Letícia da Cunha Guida, Leonardo Gomes, Maria Elisabeth Lopes Moreira, Elizeu Fagundes de Carvalho, Cynthia Chester Cardoso, Marcelo Muller, Ana Paula Dinis Ano Bom, Patrícia Cristina da Costa Neves, Zilton Vasconcelos, Milton Ozório Moraes

Host factors that influence Congenital Zika Syndrome (CZS) outcome remain elusive. Interferons have been reported as the main antiviral factor in Zika and other flavivirus infections. Here, we accessed samples from 153 pregnant women (77 without and 76 with CZS) and 143 newborns (77 without and 66 with CZS) exposed to ZIKV conducted a case-control study to verify whether interferon alfa receptor 1 (IFNAR1) and interferon lambda 2 and 4 (IFNL2/4) single nucleotide polymorphisms (SNPs) contribute to CZS outcome, and characterized placenta gene expression profile at term. Newborns carrying CG/CC genotypes of rs2257167 in IFNAR1 presented higher risk of developing CZS (OR=3.41; IC=1.35-8.60; Pcorrected=0.032). No association between IFNL SNPs and CZS was observed. Placenta from CZS cases displayed lower levels of IFNL2 and ISG15 along with higher IFIT5. The rs2257167 CG/CC placentas also demonstrated high levels of IFIT5 and inflammation-related genes. We found CZS to be related with exacerbated type I IFN and insufficient type III IFN in placenta at term, forming an unbalanced response modulated by the IFNAR1 rs2257167 genotype. Despite of the low sample size se findings shed light on the host-pathogen interaction focusing on the genetically regulated type I/type III IFN axis that could lead to better management of Zika and other TORCH (Toxoplasma, Others, Rubella, Cytomegalovirus, Herpes) congenital infections.