scholarly journals Multimerization of Zika Virus-NS5 causes a ciliopathy and forces premature neurogenesis

2019 ◽  
Author(s):  
Murielle Saade ◽  
Diego S Ferrero ◽  
José Blanco-Ameijeiras ◽  
Elena Gonzalez-Gobartt ◽  
Victor M Ruiz-Arroyo ◽  
...  
Keyword(s):  
Zika Virus ◽  
Primary Cilia ◽  
Neural Progenitor Cells ◽  
Fetal Brain ◽  
Ependymal Cells ◽  
Host Proteins ◽  
Cellular Events ◽  
Neural Tissues ◽  
Congenital Zika Syndrome ◽  
Congenital Microcephaly

AbstractZika virus (ZikV) is a flavivirus that infects neural tissues, causing congenital microcephaly. ZikV has evolved multiple mechanisms to restrict proliferation and enhance cell death, although the underlying cellular events involved remain unclear. Here we show that the ZikV-NS5 protein interacts with host proteins at the base of the primary cilia in neural progenitor cells, causing an atypical non-genetic ciliopathy and premature neuron delamination. Furthermore, in human microcephalic fetal brain tissue, ZikV-NS5 persists at the base of the motile cilia in ependymal cells, which also exhibit a severe ciliopathy. While the enzymatic activity of ZikV-NS5 appears to be dispensable, the Y25, K28 and K29 residues in the protein, that are involved in NS5-oligomerization, are essential for the localization and interaction with components of the cilium base, promoting ciliopathy and premature neurogenesis. These findings lay the foundation to develop therapies that target ZikV-NS5-multimerization, preventing the developmental malformations associated with congenital Zika syndrome

scholarly journals Case Report: Congenital Arthrogryposis and Unilateral Absences of Distal Arm in Congenital Zika Syndrome

2021 ◽  
Vol 8 ◽  
Author(s):  
Silvina Noemí Contreras-Capetillo ◽  
José Rafael Palma-Baquedano ◽  
Nina Valadéz-González ◽  
Pablo Manrique-Saide ◽  
Hirian Alonso Moshe Barrera-Pérez ◽  
...  
Keyword(s):  
Zika Virus ◽  
Neural Progenitor Cells ◽  
Umbilical Artery ◽  
Fetal Brain ◽  
Vascular Events ◽  
Vascular Abnormalities ◽  
Clinical Observations ◽  
Vascular Flow ◽  
Congenital Zika Syndrome ◽  
The Right

Zika virus was recognized as a teratogen in 2015, when prenatal Zika infection was associated with neonatal microcephaly. The transmission, virulence, tropism, and consequences of Zika virus infection during pregnancy are currently studied. Decreased neural progenitor cells, arrest in neuronal migration and/or disruption of the maturation process of the fetus central nervous system have been associated. Congenital Zika Syndrome produces a fetal brain disruption sequence resulting in structural brain abnormalities, microcephaly, intracranial calcifications, fetal akinesia and arthrogryposis. Vascular abnormalities like unique umbilical artery and decreased cerebral vascular flow have been described in some patients. This article reports a Zika positive patient with sequence of fetal brain disruption, arthrogryposis and absence of distal third of the right forearm. This report expands the clinical observations of congenital Zika syndrome that may be related to disruptive vascular events.

Zika Virus Infection in Pregnancy, Microcephaly, and Maternal and Fetal Health: What We Think, What We Know, and What We Think We Know

2016 ◽  
Vol 141 (1) ◽  
pp. 26-32 ◽  
Author(s):  
Maria Gabriela Alvarado ◽  
David A. Schwartz
Keyword(s):  
Brain Damage ◽  
Zika Virus ◽  
Experimental Studies ◽  
Fetal Brain ◽  
Zikv Infection ◽  
Host Genetics ◽  
Fetal Infection ◽  
Congenital Zika Syndrome ◽  
Experimental Laboratory ◽  
Congenital Microcephaly

Context.—The global epidemic of Zika virus (ZIKV) infection has emerged as an important public health problem affecting pregnant women and their infants. Objectives.—To review the causal association between ZIKV infection during pregnancy and intrauterine fetal infection, microcephaly, brain damage, congenital malformation syndrome, and experimental laboratory models of fetal infection. Many questions remain regarding the risk factors, pathophysiology, epidemiology, and timing of maternal-fetal transmission and disease. These include mechanisms of fetal brain damage and microcephaly; the role of covariables, such as viral burden, duration of viremia, and host genetics, on vertical transmission; and the clinical and pathologic spectrum of congenital Zika syndrome. Additional questions include defining the potential long-term physical and neurobehavioral outcomes for infected infants, whether maternal or fetal host genetics influence the clinical outcome, and whether ZIKV infection can cause maternal morbidity. Finally, are experimental laboratory and animal models of ZIKV infection helpful in addressing maternal-fetal viral transmission and the development of congenital microcephaly? This communication provides current information and attempts to address some of these important questions. Data Sources.—Comprehensive review of published scientific literature. Conclusions.—Recent advances in epidemiology, clinical medicine, pathology, and experimental studies have provided a great amount of new information regarding vertical ZIKV transmission and the mechanisms of congenital microcephaly, brain damage, and congenital Zika syndrome in a relatively short time. However, much work still needs to be performed to more completely understand the maternal and fetal aspects of this new and emerging viral disease.

scholarly journals Association of arthrogryposis in neonates with microcephaly due to Zika virus - a case serie

2016 ◽  
Vol 16 (suppl 1) ◽  
pp. S83-S88 ◽  
Author(s):  
Ana Catarina Matos Ishigami Alvino ◽  
Luísa Rocha Medeiros de Mello ◽  
Jucille do Amaral Meneses Meira de Oliveira
Keyword(s):  
Zika Virus ◽  
Joint Stiffness ◽  
The Body ◽  
Maternal Infection ◽  
Infection Period ◽  
Vaginal Deliveries ◽  
Congenital Zika Syndrome ◽  
Motor Nerves ◽  
Congenital Microcephaly ◽  
Peripheral Motor

Abstract Introduction: in 2015 an increasing number of congenital microcephaly cases were associated to maternal infection due to Zika virus. Some of these patients presented other alterations and arthrogryposis was the most frequently found. Arthrogryposis is defined as congenital joint contractures involving at least two different areas of the body. Description: arthrogryposis was found in 18 patients with congenital microcephaly due to Zika virus. 67% of the cases were vaginal deliveries. 50% of resuscitation performed in the delivery room was necessary. The mean birth weight was 2.371g, gestational age was 39 weeks and the head circumference was 28.3cm, 15 (83%) of these patients presented severe microcephaly. All the neonates resulted in concomitant hip joints and some also had knees, ankles and wrists affected. Nine neonates (50%) presented an early respiratory distress and four (22%) died due to respiratory failure. Discussion: the neurological result found in patients with Congenital Zika Syndrome seems to be associated to the maternal infection period. During the early stages of embryogenesis, in addition to microcephaly, could be related to the peripheral motor nerves leading to fetal akinesia, joint stiffness and arthrogryposis. These neonates tend to present greater morbimortality with the worst prognosis.

scholarly journals Clinical Outcomes of a Zika Virus Mother–Child Pair Cohort in Spain

Pathogens ◽  
2020 ◽  
Vol 9 (5) ◽  
pp. 352 ◽  
Author(s):  
Antoni Soriano-Arandes ◽  
Marie Antoinette Frick ◽  
Milagros García López-Hortelano ◽  
Elena Sulleiro ◽  
Carlota Rodó ◽  
...  
Keyword(s):  
Zika Virus ◽  
Adverse Outcomes ◽  
Zikv Infection ◽  
Child Pair ◽  
Referral Hospitals ◽  
Congenital Zika Syndrome ◽  
Endemic Areas ◽  
Neurodevelopmental Abnormalities ◽  
Congenital Microcephaly

Background: Zika virus (ZIKV) infection has been associated with congenital microcephaly and other neurodevelopmental abnormalities. There is little published research on the effect of maternal ZIKV infection in a non-endemic European region. We aimed to describe the outcomes of pregnant travelers diagnosed as ZIKV-infected in Spain, and their exposed children. Methods: This prospective observational cohort study of nine referral hospitals enrolled pregnant women (PW) who travelled to endemic areas during their pregnancy or the two previous months, or those whose sexual partners visited endemic areas in the previous 6 months. Infants of ZIKV-infected mothers were followed for about two years. Results: ZIKV infection was diagnosed in 163 PW; 112 (70%) were asymptomatic and 24 (14.7%) were confirmed cases. Among 143 infants, 14 (9.8%) had adverse outcomes during follow-up; three had a congenital Zika syndrome (CZS), and 11 other potential Zika-related outcomes. The overall incidence of CZS was 2.1% (95%CI: 0.4–6.0%), but among infants born to ZIKV-confirmed mothers, this increased to 15.8% (95%CI: 3.4–39.6%). Conclusions: A nearly 10% overall risk of neurologic and hearing adverse outcomes was found in ZIKV-exposed children born to a ZIKV-infected traveler PW. Longer-term follow-up of these children is needed to assess whether there are any later-onset manifestations.

scholarly journals ZIKV Infection Induces DNA Damage Response and Alters the Proteome of Gastrointestinal Cells

Viruses ◽  
2020 ◽  
Vol 12 (7) ◽  
pp. 771 ◽  
Author(s):  
Kathleen Glover ◽  
Kevin M. Coombs
Keyword(s):  
Neural Progenitor Cells ◽  
Congenital Abnormalities ◽  
Fetal Brain ◽  
Gastrointestinal Diseases ◽  
Human Cell Line ◽  
Therapeutic Interventions ◽  
Host Proteins ◽  
Zikv Infection ◽  
Gastrointestinal Complications

The zika virus (ZIKV) is a neurotropic virus that causes congenital abnormalities in babies when they are infected in utero. Some studies have reported these congenital abnormalities result from ZIKV attacking neural progenitor cells within the brain which differentiate into neurons, oligodendrocytes, and astrocytes. Each of these glial cells play important roles during development of the fetal brain. In addition to ZIKV-induced congenital abnormalities, infected patients experience gastrointestinal complications. There are presently no reports investigating the role of this virus at the proteomic level in gastrointestinal associated cells, so we conducted an in vitro proteomic study of ZIKV-induced changes in Caco-2, a colon-derived human cell line which is known to be permissive to ZIKV infection. We used SomaScan, a new aptamer-based proteomic tool to identify host proteins that are dysregulated during ZIKV infection at 12, 24, and 48 h post-infection. Bioinformatic analyses predicted that dysregulation of differentially-regulated host proteins results in various gastrointestinal diseases. Validation of the clinical relevance of these promising protein targets will add to the existing knowledge of ZIKV biology. These potential proteins may be useful targets towards the development of therapeutic interventions.

scholarly journals 1872. Neurodevelopment in Apparently Normal Infants from Zika Virus Positive Pregnancies

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S46-S47
Author(s):  
Sarah B Mulkey ◽  
Margarita Arroyave-Wessel ◽  
Colleen Peyton ◽  
Dorothy Bulas ◽  
Gilbert Vezina ◽  
...  
Keyword(s):  
Zika Virus ◽  
Infant Development ◽  
Brain Mri ◽  
Fetal Brain ◽  
In Utero ◽  
Cranial Ultrasound ◽  
Neurodevelopmental Delay ◽  
Congenital Zika Syndrome ◽  
Z Scores ◽  
Us Findings

Abstract Background Congenital Zika syndrome (CZS) is seen in 5–12% of newborns from Zika virus (ZIKV)-infected pregnancies and includes severe neurologic abnormalities. However, the majority of ZIKV-exposed newborns do not have CZS. The risk for neurodevelopmental impairment for infants without CZS following in utero ZIKV is not well known. The objective was to determine whether infants without CZS exposed to ZIKV in utero, have normal neurodevelopment. Methods We performed a longitudinal study of neurodevelopment in Colombia for infants exposed to ZIKV in utero who had a normal fetal brain MRI (Mulkey et al, JAMA Peds 2019) and normal head circumference at birth. Infant development was assessed by the Warner Initial Developmental Evaluation of Adaptive and Functional Skills (WIDEA) and the Alberta Infant Motor Scale (AIMS) between 6 and 18 months of age. In-person training was done by a neurologist. The AIMS were video-recorded and scored centrally. Interrater reliability for the novel method of video-based AIMS was determined. WIDEA and AIMS scores were converted to Z-scores compared with normative samples. We also compared development between infants with normal and nonspecific findings on cranial ultrasound (US). Results Seventy-two non-CZS infants had neurodevelopmental tests; 40 were at a mean (SD) of 5.7 (0.9) months and 66 were at 13.5 (3.2) months of age. Thirty-four had two assessments. The total WIDEA, social cognition, and mobility domain scores became more abnormal with postnatal age (figure). The AIMS scores were similar to the normative sample. Three infants had an AIMS score < 2 SD’s below the norm. On cranial US, 19 infants (26%) had a nonspecific finding (lenticulostriate vasculopathy, choroid plexus cysts, subependymal cysts, and/or calcification). Infants with a US finding had a lower WIDEA mobility score than infants with normal US (P = .054). There was a trend toward lower AIMS scores in infants with US findings compared with infants with normal US (P = .26). AIMS Interrater agreement on video-based scoring was good (ICC = 0.73, 95% CI 0.42, 0.87). Conclusion ZIKV-exposed infants without CZS are at risk for neurodevelopmental delay. Nonspecific cranial US findings may represent mild ZIKV-related injury. Long-term neurodevelopmental follow-up is important for all ZIKV-exposed infants. Disclosures All Authors: No reported Disclosures.

scholarly journals In Vitro Zika Virus Infection of Human Neural Progenitor Cells: Meta-Analysis of RNA-Seq Assays

2020 ◽  
Vol 8 (2) ◽  
pp. 270 ◽  
Author(s):  
Rossella Gratton ◽  
Paola Maura Tricarico ◽  
Almerinda Agrelli ◽  
Heverton Valentim Colaço da Silva ◽  
Lucas Coêlho Bernardo ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Zika Virus ◽  
Neural Progenitor Cells ◽  
Meta Analysis ◽  
Fetal Brain ◽  
Neural Progenitor ◽  
Gene Expression Omnibus ◽  
Human Neural Progenitor Cells ◽  
Apoptosis Pathways

The Zika virus (ZIKV) is an emergent arthropod-borne virus (arbovirus) responsible for congenital Zika syndrome (CZS) and a range of other congenital malformations. Evidence shows that ZIKV infects human neural progenitor cells (hNPCs) in the fetal brain, prompting inflammation and tissue damage/loss. Despite recent advances, little is known about the pathways involved in CZS pathogenesis. We performed a meta-analysis, gene ontology (GO), and pathway analysis of whole transcriptome studies with the aim of clarifying the genes and pathways potentially altered during hNPCs infection with ZIKV. We selected three studies (17 samples of infected hPNCs compared to hPNCs uninfected controls) through a systematic search of the Gene Expression Omnibus (GEO) database. The raw reads were trimmed, counted, and normalized. Next, we performed a rank product meta-analysis to detect consistently differentially expressed genes (DEGs) in these independent experiments. We detected 13 statistically significant DEGs. GO ontology and reactome analysis showed an enrichment of interferon, pro-inflammatory, and chemokines signaling and apoptosis pathways in ZIKV-infected cells. Moreover, we detected three possible new candidate genes involved in hNPCs infection: APOL6, XAF1, and TNFRSF1. Our results confirm that interferon (IFN) signaling dominates the ZIKV response, and that a crucial contribution is given by apoptotic pathways, which might elicit the CZS phenotype.

scholarly journals Strain-Dependent Consequences of Zika Virus Infection and Differential Impact on Neural Development

Viruses ◽  
2018 ◽  
Vol 10 (10) ◽  
pp. 550 ◽  
Author(s):  
Forrest Goodfellow ◽  
Katherine Willard ◽  
Xian Wu ◽  
Shelley Scoville ◽  
Steven Stice ◽  
...  
Keyword(s):  
Progenitor Cells ◽  
Neural Development ◽  
Zika Virus ◽  
Neural Progenitor Cells ◽  
Neural Progenitor ◽  
Experimental Models ◽  
Neurological Dysfunction ◽  
Congenital Zika Syndrome ◽  
Extensive Cell ◽  
And Migration

Maternal infection with Zika virus (ZIKV) during pregnancy can result in neonatal abnormalities, including neurological dysfunction and microcephaly. Experimental models of congenital Zika syndrome identified neural progenitor cells as a target of viral infection. Neural progenitor cells are responsible for populating the developing central nervous system with neurons and glia. Neural progenitor dysfunction can lead to severe birth defects, namely, lissencephaly, microcephaly, and cognitive deficits. For this study, the consequences of ZIKV infection in human pluripotent stem cell-derived neural progenitor (hNP) cells and neurons were evaluated. ZIKV isolates from Asian and African lineages displayed lineage-specific replication kinetics, cytopathic effects, and impacts on hNP function and neuronal differentiation. The currently circulating ZIKV isolates exhibit a unique profile of virulence, cytopathic effect, and impaired cellular functions that likely contribute to the pathological mechanism of congenital Zika syndrome. The authors found that infection with Asian-lineage ZIKV isolates impaired the proliferation and migration of hNP cells, and neuron maturation. In contrast, the African-lineage infections resulted in abrupt and extensive cell death. This work furthers the understanding of ZIKV-induced brain pathology.

scholarly journals Placental Morphologic Similarities Between ZIKV-Positive and HIV-Positive Pregnant Women

2021 ◽  
Vol 12 ◽  
Author(s):  
Daiane Cristine Martins Ronchi ◽  
Mineia Alessandra Scaranello Malaquias ◽  
Patrícia Zadorosnei Rebutini ◽  
Letícia Arianne Panini do Carmo ◽  
Plínio Cézar Neto ◽  
...  
Keyword(s):  
Pregnant Women ◽  
Zika Virus ◽  
Hiv Positive ◽  
Control Group ◽  
Hofbauer Cells ◽  
Congenital Zika Syndrome ◽  
Global Concern ◽  
Conventional Microscopy ◽  
Congenital Microcephaly ◽  
The Relationship

Zika virus (ZIKV) caused global concern due to Brazil's unexpected epidemic, and it was associated with congenital microcephaly and other gestational intercurrences. The study aimed to analyze the placenta morphometric changes of ZIKV-infected pregnant women (ZIKV group; n = 23) compared to placentas of HIV-infected (HIV group; n = 24) and healthy pregnant women (N-control group; n = 22). It also analyzed the relationship between the morphometric results and pathological alterations on conventional microscopy, gestational trimester of infection, and presence of the congenital Zika syndrome (CZS). There was a significant increase in area (p = 0.0172), as well as a higher number of knots (p = 0.0027), sprouts (p &lt; 0.0001), and CD163 +Hofbauer cells (HCs) (p &lt; 0.0001) in the ZIKV group compared to the N-control group, suggesting that villous dysmaturity and HCs hyperplasia could be associated with ZIKV infections. The HIV group had a higher area (p &lt; 0.0001), perimeter (p = 0.0001), sprouts (p &lt; 0.0001), and CD163 + HCs (p &lt; 0.0001) compared to the N-control group, demonstrating that the morphometric abnormalities found in the ZIKV and HIV group are probably similar. However, when ZIKV and HIV groups are compared, it was observed a higher number of sprouts (p = 0.0066) and CD163+ HCs (p &lt; 0.0001) in the first one, suggesting that placental ZIKV congenital changes could be more pronounced.

scholarly journals Is Zika Virus an Emerging TORCH Agent? An Invited Commentary

2017 ◽  
Vol 8 ◽  
pp. 1178122X1770899 ◽  
Author(s):  
Mohammad Zare Mehrjardi
Keyword(s):  
Public Health ◽  
Zika Virus ◽  
Imaging Modality ◽  
Fold Increase ◽  
Northeastern Brazil ◽  
Caribbean Region ◽  
Fetal Ultrasound ◽  
Zikv Infection ◽  
Congenital Zika Syndrome ◽  
Congenital Microcephaly

Zika virus (ZIKV) is a mosquito-borne arbovirus from the family Flaviviridae, which had caused some epidemics since its discovery in 1947 without any significant impacts on public health. In 2015, however, a 20-fold increase in congenital microcephaly cases in northeastern Brazil was attributed to prenatally acquired ZIKV infection. Traditionally, TORCH agents have 4 common characteristics including causing a mild illness in infected mother, vertical transmission to fetus, developing several anomalies in the affected fetus, and in some instances, maternal therapy may not ameliorate fetal prognosis. Prenatal ZIKV infection has shown the aforementioned characteristics during the recent epidemics in South America and the Caribbean region; therefore, it should be considered as an emerging TORCH agent that may seriously threaten public health. Fetal ultrasound can be used as a safe, inexpensive, and easy-to-access imaging modality for detecting suspicious cases of congenital Zika syndrome in utero and suggesting confirmatory diagnostic examinations to these patients.

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