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Congenital Zika Syndrome Is Associated With Interferon Alfa Receptor 1.

ABSTRACT: 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.

SUBMITTER: Azamor T

PROVIDER: S-EPMC8657619 | biostudies-literature | 2021

REPOSITORIES: biostudies-literature

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Congenital Zika Syndrome Is Associated With Interferon Alfa Receptor 1.

Azamor Tamiris T Cunha Daniela Prado DP da Silva Andréa Marques Vieira AMV Bezerra Ohanna Cavalcanti de Lima OCL Ribeiro-Alves Marcelo M Calvo Thyago Leal TL Kehdy Fernanda de Souza Gomes FSG Manta Fernanda Saloum de Neves FSN Pinto Thiago Gomes de Toledo TGT Ferreira Laís Pereira LP Portari Elyzabeth Avvad EA Guida Letícia da Cunha LDC Gomes Leonardo L Moreira Maria Elisabeth Lopes MEL de Carvalho Elizeu Fagundes EF Cardoso Cynthia Chester CC Muller Marcelo M Ano Bom Ana Paula Dinis APD Neves Patrícia Cristina da Costa PCDC Vasconcelos Zilton Z Moraes Milton Ozório MO

Frontiers in immunology 20211125

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 (<i>IFNAR1</i>) and interferon lambda 2 and 4 (<i>IFNL2/4</i>) single nucleotide polymorphisms (SNP ...[more]

PMID: 34899713

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Project description:BackgroundChildren with in utero Zika virus (ZIKV) exposure without congenital Zika syndrome (CZS) are at risk for abnormal neurodevelopment. Preschool-age outcomes for children with antenatal ZIKV exposure have not yet been established.MethodsChildren with in utero ZIKV exposure and non-exposed controls had neurodevelopmental evaluations at age 3-5 years in Sabanalarga, Colombia. Cases did not have CZS and were previously evaluated prenatally through age 18 months. Controls were born before ZIKV arrival to Colombia. Neurodevelopmental assessments included Pediatric Evaluation of Disability Inventory (PEDI-CAT), Behavior Rating Inventory of Executive Function (BRIEF-P), Bracken School Readiness Assessment (BSRA), and Movement Assessment Battery for Children (MABC). Family demographics and child medical history were recorded.ResultsFifty-five ZIKV-exposed children were evaluated at mean age 3.6 years and 70 controls were evaluated at 5.2 years. Family demographics were similar between groups. BRIEF-P t-scores were higher for cases than controls in shift and flexibility domains. Cases had lower PEDI-CAT mobility t-scores compared to controls. There was no difference in MABC between groups. In 11% of cases and 1% of controls, parents reported child mood problems.ConclusionsChildren with in utero ZIKV exposure without CZS may demonstrate emerging differences in executive function, mood, and adaptive mobility that require continued evaluation.ImpactPreschool neurodevelopmental outcome in children with in utero Zika virus exposure is not yet known, since the Zika virus epidemic occurred in 2015-2017 and these children are only now entering school age. This study finds that Colombian children with in utero Zika virus exposure without congenital Zika syndrome are overall developing well but may have emerging differences in executive function, behavior and mood, and adaptive mobility compared to children without in utero Zika virus exposure. Children with in utero Zika virus exposure require continued multi-domain longitudinal neurodevelopmental evaluation through school age.

Dataset Information

Congenital Zika Syndrome Is Associated With Interferon Alfa Receptor 1.

Publications

Congenital Zika Syndrome Is Associated With Interferon Alfa Receptor 1.

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