Congenital Zika Syndrome Is Associated With Interferon Alfa Receptor 1.
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ABSTRACT:
SUBMITTER: Azamor T
PROVIDER: S-EPMC8657619 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Zika virus (ZIKV) infection during pregnancy is associated with a spectrum of developmental impairments known as congenital Zika syndrome (CZS). The prevalence of this syndrome varies across ZIKV endemic regions, suggesting that its occurrence could depend on cofactors. Here, we evaluate the relevance of protein malnutrition for the emergence of CZS. Epidemiological data from the ZIKV outbreak in the Americas suggest a relationship between undernutrition and cases of microcephaly. To experimentally examine this relationship, we use immunocompetent pregnant mice, which were subjected to protein malnutrition and infected with a Brazilian ZIKV strain. We found that the combination of protein restriction and ZIKV infection leads to severe alterations of placental structure and embryonic body growth, with offspring displaying a reduction in neurogenesis and postnatal brain size. RNA-seq analysis reveals gene expression deregulation required for brain development in infected low-protein progeny. These results suggest that maternal protein malnutrition increases susceptibility to CZS.
| S-EPMC6954064 | biostudies-literature
Project description:BackgroundCongenital syndrome of Zika virus (CSZV) is associated with neuromotor and cognitive developmental disorders, limiting the independence and autonomy of affected children and high susceptibility to complications, so palliative care needs to be discussed and applied.AimTo identify factors associated with emergency visits and hospitalizations of patients with CSZV and clinical interventions performed from the perspective of palliative care.DesignThis is a cross-sectional study with bidirectional longitudinal component. Data were collected between May and October 2017 through the review of medical records and interviews with relatives of patients hospitalized.Setting/participantsThe study was developed in a tertiary care hospital involving patients with confirmed CSZV born as of August 2015 and followed up until October 2017. Patients under investigation were excluded.Results145 patients were followed up at the specialized outpatient clinic, 92 (63.5%) were consulted at least once in the emergency room, and 49% had already been hospitalized, with the main reason being neurological causes, while 24.1% had never required any emergency visit or hospitalization. No risk factors were associated with the occurrence of consultations or hospitalizations. Such events happened at an early age and were accompanied by a high number of invasive procedures and interventions. An approach in palliative care was only identified in two hospitalized patients.ConclusionsFor the patient with known severe malformations caused by congenital infection by the Zika virus with indication of palliative care, this approach could be used in order to allow life without suffering and disproportionate invasive method.
| S-EPMC6201378 | biostudies-literature
Project description:ObjectiveTo describe the neurological and neurodevelopmental outcomes of children with Congenital Zika Syndrome (CZS) associated microcephaly beyond 2 years of age.MethodWe followed children with CZS-associated microcephaly in an outpatient clinic in Salvador, Brazil. Neurological and neurodevelopmental assessments were performed using the Hammersmith Infant Neurological Examination (HINE) and Bayley Scales of Infant and Toddler Neurodevelopment (Bayley-III) respectively.ResultsOf the 42 children included, 19 were male (45.2%); median (interquartile range) age at neurological evaluation was 28 (25-32) months, and 36 (85.7%) had severe microcephaly. HINE and Bayley-III results were completed for 35/42 (83.3%) and 33/42 (78.5%) children respectively. Bayley-III identified a severe developmental delay in 32/33 (97.0%) children while 1/33 (3.0%) had only a mild delay. In the multivariable analysis, we found that Bayley-III and HINE scores were correlated. Better HINE scores were associated with higher Bayley-III cognitive raw scores (β = 0.29; CI 95% = 0.02-0.57) and motor raw scores (β = 0.43; CI 95% = 0.04-0.82) after adjusting for head circumference, prematurity, and age at neurodevelopmental evaluation. Furthermore, we found that greater head circumference at follow up was associated with higher cognitive (β = 1.27; CI 95% = 0.01-2.53) and motor raw scores (β = 2.03; CI 95% = 0.25-3.81).ConclusionChildren with CZS-associated microcephaly demonstrate severe neurodevelopmental delays and slower growth rates than their peers over time. Still, they have remarkably heterogeneous neurodevelopmental profiles according to neurological exam scores which correlate with their long-term outcomes. We found that HINE scores effectively captured the heterogeneity of neurological capabilities among these children and could be predictive of cognitive and motor development progress.
| S-EPMC8443077 | biostudies-literature
Project description:In this study, we analyzed by a shotgun proteomic approach the amniotic fluid of pregnant women infected with Zika carrying microcephalic (ZIKV+M+) or healthy fetuses (ZIKV+M-) compared to Zika negative controls (ZIKV-M-) to identify and understand the biological process and pathways affected by CZS development. Up-abundant proteins in the ZIKV+M- group showed enrichment mainly in the extracellular matrix (ECM) structure and organization. The innate immune system (i.e. neutrophil degranulation) and fibrin clot formation processes were dysregulated in the ZIKV+M+ group, with an increase in the abundance of proteins associated with these biological processes. In both groups, a decrease in the abundance of proteins associated with neutrophil degranulation was observed. ZIKV+M+ group presented a decrease of abundance in the dysregulated extracellular matrix proteins compared to ZIKV+M-. These results could suggest that the development of microcephalic or healthy phenotypes is more associated with the ECM and immune system protein abundances than the dysregulated processes in each group.
2024-07-02 | PXD023776 | Pride
Project description:BackgroundThe signs and symptoms of Zika virus infection are usually mild and self-limited. However, the disease has been linked to neurological complications such as Guillain-Barré syndrome and peripheral nerve involvement, and also to abortion and fetal deaths due to vertical transmission, resulting in various congenital malformations in newborns, including microcephaly. This review aimed to describe the o signs and symptoms that characterize the congenital Zika syndrome.Methods and findingsA systematic review was performed with a protocol and described according to the recommendations of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. The search strategy yielded 2,048 studies. After the exclusion of duplicates and application of inclusion criteria, 46 studies were included. The main signs and symptoms associated with the congenital Zika syndrome were microcephaly, parenchymal or cerebellar calcifications, ventriculomegaly, central nervous system hypoplasia or atrophy, arthrogryposis, ocular findings in the posterior and anterior segments, abnormal visual function and low birthweight for gestational age.ConclusionsZika virus infection during pregnancy can cause a series of changes in the growth and development of children, while impacting the healthcare system due to the severity of cases. Our findings outline the disease profile in newborns and infants and may contribute to the development and updating of more specific clinical protocols.
| S-EPMC7737899 | biostudies-literature
Project description:Zika virus (ZIKV) infects pregnant women and causes devastating congenital zika syndrome (CZS). How the virus is vertically transmitted to the fetus and induces neuronal loss remains unclear. We previously reported that Pellino (Peli)1, an E3 ubiquitin ligase, promotes p38MAPK activation in microglia and induction of lethal encephalitis by facilitating the replication of West Nile virus (WNV), a closely related flavivirus. Here, we found that Peli1 expression was induced on ZIKV-infected human monocytic cells, peripheral blood mononuclear cells, human first-trimester placental trophoblasts, and neural stem cell (hNSC)s. Peli1 mediates ZIKV cell attachment, entry and viral translation and its expression is confined to the endoplasmic reticulum. Moreover, Peli1 mediated inflammatory cytokine and chemokine responses and induced cell death in placental trophoblasts and hNSCs. ZIKV-infected pregnant mice lacking Peli1 signaling had reduced placental inflammation and tissue damage, which resulted in attenuated congenital abnormalities. Smaducin-6, a membrane-tethered Smad6-derived peptide, blocked Peli1-mediated NF-?B activation but did not have direct effects on ZIKV infection. Smaducin-6 reduced inflammatory responses and cell death in placental trophoblasts and hNSCs, and diminished placental inflammation and damage, leading to attenuated congenital malformations in mice. Collectively, our results reveal a novel role of Peli1 in flavivirus pathogenesis and suggest that Peli1 promotes ZIKV vertical transmission and neuronal loss by mediating inflammatory cytokine responses and induction of cell death. Our results also identify Smaducin-6 as a potential therapeutic candidate for treatment of CZS.
| S-EPMC7297310 | biostudies-literature
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.
| S-EPMC10227180 | biostudies-literature
Project description:BACKGROUND:We aim to investigate possible maternal- and pregnancy-related factors associated with the development of Congenital Zika Syndrome (CZS) in children of mothers with probable gestational infection. METHODS:This case-control study, we recruited mother-infant pairs between May 2015 and October 2017 in a pediatric infectious disease clinic in Rio de Janeiro. Inclusion criteria required either that the mother reported Zika infection symptoms during pregnancy or that the infant presented with clinical or imaging features of the CZS. Exclusion criteria included detection of an alternative cause for the patient's presentation or negative polymerase chain reaction assays for Zika in all specimens tested within 12?days from the beginning of maternal symptoms. Infants with CZS (CDC definition) were selected as cases and infants without CZS, but with probable maternal Zika virus infection during pregnancy, were selected as controls. Maternal and pregnancy-related informations were collected and their relationship to the presence of congenital anomalies due to CZS was assessed by Fisher exact or Mann-Whitney test. RESULTS:Out of the 42 included neonates, 24 (57.1%) were diagnosed with CZS (cases). The mean maternal age at the birth was 21?years old. The early occurrence of maternal symptoms during pregnancy was the only variable associated with CZS (odds ratio?=?0.87, 95% CI: 0.78-0.97). Case's mothers presented symptoms until the 25th week of gestational age (GA), while control's mothers presented until 36th weeks of GA. Income; illicit drug, alcohol, or tobacco use during pregnancy; other infections during pregnancy (including previous dengue infection) were not associated with CZS. CONCLUSIONS:Our study corroborates the hypothesis that Zika virus infection earlier in pregnancy is a risk factor to the occurrence of congenital anomalies in their fetuses.
| S-EPMC6431070 | biostudies-literature
Project description:Congenital Zika syndrome (CZS) is characterized by a diverse group of congenital malformations induced by ZIKV infection during pregnancy. Type III interferons have been associated with placental immunity against ZIKV and restriction of vertical transmission in mice, and non-coding single-nucleotide polymorphisms (SNPs) on these genes are well known to influence susceptibility to other viral infections. However, their effect on ZIKV pathogenesis has not yet been explored. To investigate whether maternal non-coding SNPs at IFNL genes are associated with CZS, 52 women infected with ZIKV during pregnancy were enrolled in a case-control association study. A total of 28 women were classified as cases and 24 as controls based on the presence or absence of CZS in their infants, and seven Interferon-λ non-coding SNPs (rs12980275, rs8099917, rs4803217, rs4803219, rs8119886, rs368234815, rs12979860) were genotyped. The results of logistic regression analyses show an association between the G allele at rs8099917 and increased susceptibility to CZS under a log-additive model (adjustedOR = 2.80; 95%CI = 1.14-6.91; p = 0.02), after adjustment for trimester of infection and genetic ancestry. These results provide evidence of an association between Interferon-λ SNPs and CZS, suggesting rs8099917 as a promising candidate for further studies on larger cohorts.
| S-EPMC8622836 | biostudies-literature
Project description:GENETIC EVALUATION IN CHILDREN WITH EYE ANOMALIES ASSOCIATED WITH CONGENITAL ZIKA SYNDROME
| PRJEB40869 | ENA