Congenital Zika Virus Syndrome Research Articles

How Essential Oils Affect Children with Congenital Zika Virus Syndrome (CZVS)

Introduction: Within the field of dentistry, essential oils are well-known and extensively researched; eugenol is one of the most used, which until recently characterized the predominant smell of dental offices. Children with congenital Zika virus syndrome (CZVS) have various impairments, and in the dental area, the vast majority exhibit underdevelopment of the stomatognathic system compared to established normality standards. Many use various medications, such as anticonvulsants, muscle relaxants, sedatives, neuroleptics, among others, to control symptoms. These drug interactions can trigger involuntary muscle movements, including bruxism. There are several treatment proposals for teeth grinding and clenching, including appliance therapy, emotional therapies, medication, and also aromatherapy. Material and method: Syndromic and bruxist children were selected through validated questionnaires and clinical examination. A convenience sample of 19 syndromic children from Maceió was divided into two random groups: group 1 received a blend of essential oils, and group 2 received a control oil. They were instructed to apply it topically to the masseter, temples, and cervical area twice a day for two months. Sleep analysis was carried out through a questionnaire with 15 questions plus filling out a sleep chart for three days and collecting saliva in Salivette tubes for cortisol evaluation, with both data sets collected pre and post-use of essential oils. Discussion: Previous studies report that individuals with cognitive difficulties are more prone to bruxism due to spasticity, however, they are not definitive according to other studies. There are other factors such as stress, depression, external environmental stimuli that can influence this condition, in addition to the drug interaction they use to alleviate symptoms such as seizures, drooling, muscle spasms, muscle stiffness, insomnia. The etiology of bruxism is still considered multifactorial, requiring a multidisciplinary clinical team for more effective treatment. The use of essential oils as a stress and insomnia reliever is reported in studies with satisfactory results, being observed in this research. Result: In the finalization phase. Conclusion: Given the above, the proposal was to evaluate the efficacy of using essential oils in syndromic and bruxist children. Although we cannot confirm results yet, there are reports from mothers who evaluated the initiative positively, corroborating in some way the alleviation of symptoms and drug interactions, providing more emotional and physical comfort for those involved. However, more clinical trials are still necessary regarding the safety and efficacy aspects of essential oils.

Experience of mothers of children affected by Congenital Zika Virus Syndrome

This study aims to know the experience of mothers of children affected by Congenital Zika Virus Syndrome (CZS) in a city in northern Minas Gerais. This is a research with a qualitative approach. For the treatment of the data was performed the Content Analysis proposed by Bardin. The diagnosis of the child with CZS caused in women the loss/mourning of the idealized child and the confrontation of the reality of the real child. This new perspective demands of women, their children and their support network a new march aimed at seeking treatment and improving quality of life. The experiences reported may contribute to the qualification of health services that deal directly with children with CZS, as it can be an important tool for guiding and evaluating the management and implementation of health care aimed at the healthy development of these children and promoting the quality of life of their entire family.

Construction of exosome-loaded LL-37 and its protection against zika virus infection

Zika virus (ZIKV) is an enveloped, single-stranded and positive-stranded RNA virus of the genus Flavivirus in the family Flaviviridae. ZIKV can cross the placental barrier and infect the fetus, causing microcephaly, congenital ZIKV syndrome, and even fetal death. ZIKV infection can also lead to testicular damage and male sterility. But no effective drugs and vaccines are available up to now. Previous studies have shown that the cathelicidin antimicrobial peptide LL-37 can protect against ZIKV infection. However, LL-37 is a secreted peptide, which can be easily degraded in vivo. We herein constructed exosome-loaded LL-37 (named LL-37-TM-exo and TM-LL-37-exo) using the transmembrane protein TM to load LL-37 onto the membrane of exosome. We found that exosome-loaded LL-37 could significantly inhibit ZIKV infection in vitro and in vivo, and LL-37-TM-exo had stronger antiviral activity than that of TM-LL-37-exo, which could significantly reduce ZIKV-induced testicular injury and sperm injury, and had broad-spectrum antiviral effect. Compared to free LL-37, exosome-loaded LL-37 showed a better serum stability, higher efficiency to cross the placental barrier, and stronger antiviral activity. The mechanism of exosome-loaded LL-37 against ZIKV infection was consistent with that of free LL-37, which could directly inactivate viral particles, reduce the susceptibility of host cells, and act on viral replication stage. Our study provides a novel strategy for the development of LL-37 against viral infection.

Caracterização do desenvolvimento infantil e linguístico de crianças acometidas da Síndrome Congênita do Zika Vírus comparadas com crianças de desenvolvimento típico

ABSTRACT Purpose: to describe the development, focusing on language, of children affected by congenital Zika syndrome and compare it with that of typically developing children. Methods: a quantitative, observational, cross-sectional, case-control study. Data from the group of children with congenital Zika virus syndrome (case) were matched for sex and age with data from the group of typically developing children without comorbidities (control). The research included 20 parents/guardians of the children in the case group and 20 parents/guardians of the children in the control group, using interview as an adapted instrument. The data underwent descriptive and inferential statistical analysis, through association tests and comparison of means, with the significance level set at 5%. Results: there was a statistical difference in motor, auditory, and language development between the groups, according to the parents' perception. Conclusion: Based on the caregivers’ reports, most of the case group communicated non-verbally through babbling, shouting, and eye contact, whereas the minority communicated through dialogue, understood simple orders, and performed imitative behaviors, symbolic play, and shared attention. On the other hand, the control group communicated through complex sentences constructed into narratives.

Characterization of linguistic development of children affected by congenital Zika virus syndrome as compared to typically developing peers

RESUMO Objetivo: descrever o desenvolvimento infantil, com enfoque na linguagem, de crianças acometidas da síndrome congênita do Zika e compará-lo com o de crianças com desenvolvimento típico. Métodos: trata-se de um estudo observacional, transversal, do tipo caso-controle, e de natureza quantitativa. Os dados do grupo de crianças com Síndrome Congênita do Zika vírus (caso) foram pareados por sexo e idade com os dados do grupo de crianças sem comorbidades e desenvolvimento típico (controle). Participaram da pesquisa, 20 responsáveis pelas crianças do grupo caso e 20 pelas crianças do grupo controle e o instrumento utilizado foi uma entrevista adaptada. Os dados foram examinados por meio de uma análise estatística descritiva e inferencial por meio de testes de associação e de comparação de médias, com nível de significância de 5%. Resultados: foi observada diferença estatística entre os grupos estudados, referente ao desenvolvimento infantil, no âmbito motor, auditivo e de linguagem, com base na percepção dos pais. Conclusão: diante das informações dos cuidadores, a comunicação da maioria do grupo caso ocorre de forma não verbal por meio de gorjeios, gritos e contato visual; e a minoria comunica-se por diálogo, compreende ordens simples, realiza condutas imitativas, brincar simbólico e tem atenção compartilhada. Diferentemente, o grupo controle comunica-se por meio de frases complexas presentes em narrativas.

Perinatal characteristics and longer-term outcomes in Brazilian children with confirmed or suspected congenital Zika infection: ZIKAction Paediatric Registry.

Despite growing scientific knowledge of Zika virus (ZIKV) infection, questions remain regarding ZIKV infection in pregnancy and congenital ZIKV syndrome (CZS). The ZIKAction Paediatric Registry is an international registry of children with documented ZIKV exposure in utero and/or with confirmed or suspected CZS. Its aim is to characterize these children (i.e., clinical, radiological, neurodevelopmental features) and describe outcomes, longer-term sequelae and management through retrospective case note review. This analysis described the maternal and perinatal characteristics of children in the Registry's Bahia arm, assessed their neuroimaging, ophthalmic, hearing and electroencephalography abnormalities by microcephaly classification and reported on hospitalisations. Children born in 2015-2018 and enrolled 2020-2021 in three public health facilities in Salvador were included. Of 129 (57% female) children, 15 (11·6%) had laboratory-confirmed congenital ZIKV infection and 114 (88·4%) suspected CZS. At delivery, 15 (11·6%) were normocephalic, 30 (23·3%) moderately microcephalic, and 84 (65·1%) severely microcephalic. Median birth head circumference z-score was -3·51 [IQR, -4·69,-2·73]. During follow-up, all children had abnormal neuroimaging, 80·3% (94/117) abnormal electroencephalogram, 62·2% (77/120) ophthalmic abnormalities, and 27·4% (34/124) hearing impairment. Microcephaly classification was significantly associated with gestational age, and ophthalmological and electroencephalography abnormalities. Of 125 children with hospitalisation data, 52 (41·6%) had been hospitalised by most recent follow-up, at median age of 15·8 [4·0, 34·4] months; infections were the leading cause. Congenital ZIKV infection is an emerging disease with a varied and incompletely understood spectrum. Continued long-term follow-up is essential to understand longer-term prognosis and to inform future health and educational needs.

Clinical and Acoustic Alterations of Swallowing in Children Exposed to Zika Virus during Pregnancy in a Cohort in Amazonas, Brazil: A Case Series Study.

Oropharyngeal dysphagia (OD) is a swallowing disorder that involves difficulty in safely passing the food bolus from the oral cavity to the stomach. OD is a common problem in children with congenital Zika virus syndrome (CZS). In this case series, we describe the clinical and acoustic alterations of swallowing in children exposed to the Zika virus during pregnancy in a cohort from Amazonas, Brazil. From July 2019 to January 2020, 22 children were evaluated, 6 with microcephaly and 16 without microcephaly. The mean age among the participants was 35 months (±4.6 months). All children with microcephaly had alterations in oral motricity, mainly in the lips and cheeks. Other alterations were in vocal quality, hard palate, and soft palate. Half of the children with microcephaly showed changes in cervical auscultation during breast milk swallowing. In children without microcephaly, the most frequently observed alteration was in lip motricity, but alterations in auscultation during the swallowing of breast milk were not observed. Regarding swallowing food of a liquid and pasty consistency, the most frequent alterations were incomplete verbal closure, increased oral transit time, inadequacy in capturing the spoon, anterior labial leakage, and increased oral transit time. Although these events are more frequent in microcephalic children, they can also be seen in non-microcephalic children, which points to the need for an indistinct evaluation of children exposed in utero to ZIKV.

Stigma perceived by mothers of children with congenital Zika virus syndrome

Objective: to understand the experiences of stigma perceived by mothers of children with congenital Zika virus syndrome and its repercussions. Methods: a qualitative study was carried out with 12 mothers who responded to semi-structured interviews. Correspondence Factor Analysis and Descending Hierarchical Classification were carried out using the IRaMuTeQ software. Results: four classes emerged that deal with the experience of perceiving stigma: Perceiving public discrimination; Stigmatizing behaviors and their repercussions; Feeling guilty and adopting coping strategies; Experiencing rejection from the father, others and feeling lonely. Conclusion: stigma is perceived by mothers of children with congenital Zika virus syndrome in affective, family, and social interactions, expressed through rejection, withdrawal and exclusion resulting in suffering for the mothers, who adopt hiding the child and self-isolation as coping strategies. Contributions to practice: nursing should identify signs of social isolation, deep sadness and stress related to the stigma of being the mother of a child with congenital Zika virus syndrome and draw up care plans to prevent maternal illness.

Synthesis of copaiba (Copaifera officinalis) oil nanoemulsion and the potential against Zika virus: An in vitro study.

Zika virus (ZIKV) has spread all over the world since its major outbreak in 2015. This infection has been recognized as a major global health issue due to the neurological complications related to ZIKV infection, such as Guillain-Barré Syndrome and Zika virus Congenital Syndrome. Currently, there are no vaccines or specific treatments for ZIKV infection, which makes the development of specific therapies for its treatment very important. Several studies have been developed to analyze the potential of compounds against ZIKV, with the aim of finding new promising treatments. Herein, we evaluate the ability of a copaiba (Copaifera officinalis) oil nanoemulsion (CNE) to inhibit ZIKV. First, the highest non-cytotoxic concentration of 180 μg/mL was chosen since this concentration maintains 80% cell viability up to 96h after treatment with CNE in VERO cells resulted from MTT assay. The intracellular uptake assay was performed, and confirmed the internalization of the nanoemulsion in cells at all times analyzed. VERO cells were infected with ZIKV and simultaneously treated with CNE and the nanoformulation without oil (ENE) at the highest non-toxic concentration. The results evaluated by plaque assay revealed a viral inhibition of 80% for CNE and 70% for ENE. A dose-dependence assay revealed that the CNE treatment demonstrated a dose-dependent response in the viral RNA levels, whereas all ENE tested concentrations exhibited a similar degree of reduction. Taken together, our results suggest CNE as a promising nano-sized platform to be further studied for antiviral treatments.

Language skills development in children with congenital Zika virus syndrome

BackgroundThe characterization of the phenotype of children with congenital Zika virus syndrome (CZS) is an ongoing process, since many characteristics can only be described with the advancing age of children providing some insights into the long-term sequelae. AimsTo describe emerging findings on the impact of CZS on language development in children with CZS in a 4-year longitudinal study. Methods and procedures39 boys and 44 girls with CZS were allocated into four groups according to age ranging from 12 to 36 months. Language development was assessed using the Early Language Milestone Scale. Outcomes and resultsVisual, expressive, and receptive auditory skills of patients were lower than expected for their age. Despite producing vowel sounds, they did not babble; despite present hearing, the majority of the children did not understand simple commands. In over 4 years of follow-up, there was no evolution in language parameters, with the children stagnating at the language skills corresponding to 3 months of age. Conclusions and implicationsMost children with CZS are not able to produce vocalic sounds, but some may be able to communicate basic needs through alternative communication. What this paper adds?Some babies with CZS died prenatally, at birth, or in the first year of life due to associated complications such as respiratory infection, dysphagia, and epilepsy. However, the functionality of the future remains uncertain for surviving babies. This study adds information about the impact of Zika Virus on the central nervous system and, consequently, the severity and complexity of the CZS language. Over 4 years of follow-up, no evolution in language parameters was observed in children with CSZ. Children with CZS demonstrate severe neurodevelopmental impairment, stagnating in language skills at the age of 3 months. In the future, some of them may be able to communicate their basic needs through alternative communication.

Disease burden of congenital Zika virus syndrome in Brazil and its association with socioeconomic data

Zika virus (ZIKV) infection became a global public health concern, causing an epidemic in Latin America from 2015 to 2016, when a sudden increase in cases of microcephaly and other congenital anomalies was observed. In 2016, the Centers for Disease Control and Prevention and the World Health Organization defined congenital Zika-associated syndrome (CZS) as a set of congenital anomalies seen in children born to mothers with a history of gestational Zika fever, who have microcephaly as the most prevalent clinical sign. In order to describe the magnitude of CZS in Brazil, this study estimated the burden of disease due to CZS in Brazil using the disability-adjusted life years (DALY) indicator and other frequency measures, such as incidence and mortality rate, during the years 2015–2020. The association of these indicators with socioeconomic variables was also evaluated using Spearman's correlation coefficient. Choropleth maps were used to evaluate the spatial distribution of the indicators evaluated and the spatial autocorrelation was verified by the Bivariate Moran Local Index. From 2015 to 2020, 3,591 cases of CZS were confirmed in Brazil, with an incidence of 44.03 cases per 1000 live births, and a specific mortality of 12.35 deaths per 1000 live births. A global loss of 30,027.44 DALYs was estimated from 2015 to 2020. The Northeast region had the highest values for all health indicators assessed. Spatial correlation and autocorrelation analyses showed significant associations between health and socioeconomic indicators, such as per capita income, Gini index, illiteracy rate and basic sanitation. The study allowed us to have access to all reported cases of CZS, showing us the possible situation of the disease in Brazil; therefore, we believe that our results can help in the understanding of future studies.

Proposal of Model for Evaluation of Viral Kinetics of African/Asian/Brazilian-Zika virus Strains (Step Growth Curve) in Trophoblastic Cell Lines.

The Zika virus (ZIKV) epidemic brought new discoveries regarding arboviruses, especially flaviviruses, as ZIKV was described as sexually and vertically transmitted. The latter shows severe consequences for the embryo/fetus, such as congenital microcephaly and deficiency of the neural system, currently known as Congenital ZIKV Syndrome (CZS). To better understand ZIKV dynamics in trophoblastic cells present in the first trimester of pregnancy (BeWo, HTR-8, and control cell HuH-7), an experiment of viral kinetics was performed for African MR766 low passage and Asian-Brazilian IEC ZIKV lineages. The results were described independently and demonstrated that the three placental cells lines are permissive and susceptible to ZIKV. We noticed cytopathic effects that are typical in in vitro viral infection in BeWo and HTR-8. Regarding kinetics, MR766lp showed peaks of viral loads in 24 and 48 hpi for all cell types tested, as well as marked cells death after peak production. On the other hand, the HTR-8 lineage inoculated with ZIKV-IEC exhibited increased viral production in 144 hpi, with a peak between 24 and 96 hpi. Furthermore, IEC had peak variations of viral production for BeWo in 144 hpi. Considering such in vitro results, the hypothesis that maternal fetal transmission is probably a way of virus transmission between the mother and the embryo/fetus is maintained.

Translation and preliminary validation of the Brazilian family resources scale in a sample of parents of children with congenital Zika virus syndrome.

Family-centered rehabilitative care optimizes outcomes for children with significant developmental disabilities. Family-centered services involve assessing family resources that promote positive developmental outcomes for children. Little is known regarding family resources in the context of caring for a child with developmental disabilities in Brazil due to an absence of validated measures. This study describes the translation and cultural adaptation of the Family Resource Scale and explored the measurement quality of the resulting measure (the Brazilian-Family Resource Scale, or B-FRS). A rigorous serial translation process that emphasized linguistic accuracy as well as cultural adaptation was utilized. The resulting 27-item B-FRS was theoretically related and reflected the contextual intent of the original measure. A four-factor scoring approach yielded acceptable internal consistency estimates for the subscales and total scale score. Overall, low levels of family resources were reported by caregivers of children with Congenital Zika Syndrome. Low family resources were associated with parental depressive and stress-related symptoms. Confirmatory factor analysis of the B-FRS in a larger sample is recommended. Practitioners in Brazil should broadly consider family needs and resources to provide family-centered care that is effective for the child and engages the family in a way that highlights their strengths and promotes positive developmental trajectories.

ZIKV Strains Elicit Different Inflammatory and Anti-Viral Responses in Microglia Cells.

In recent years, the Zika Virus (ZIKV) has caused pandemic outbreaks associated with a high rate of congenital ZIKV syndrome (CZS). Although all strains associated with worldwide outbreaks derive from the Asian lineage, the reasons for their enhanced spread and severity are not fully understood. In this study, we conducted a comparative analysis of miRNAs (miRNA-155/146a/124) and their cellular targets (SOCS1/3, SHP1, TRAF6, IRAK1), as well as pro- and anti-inflammatory and anti-viral cytokines (IL-6, TNF-α, IFN-γ, IL-10, and IFN-β) and peroxisome proliferator-activated receptor γ (PPAR-γ) expression in BV2 microglia cells infected with ZIKV strains derived from African and Asian lineages (ZIKVMR766 and ZIKVPE243). BV2 cells were susceptible to both ZIKV strains, and showed discrete levels of viral replication, with delayed release of viral particles without inducing significant cytopathogenic effects. However, the ZIKVMR766 strain showed higher infectivity and replicative capacity, inducing a higher expression of microglial activation markers than the ZIKVPE243 strain. Moreover, infection with the ZIKVMR766 strain promoted both a higher inflammatory response and a lower expression of anti-viral factors compared to the ZIKVPE243 strain. Remarkably, the ZIKKPE243 strain induced significantly higher levels of the anti-inflammatory nuclear receptor-PPAR-γ. These findings improve our understanding of ZIKV-mediated modulation of inflammatory and anti-viral innate immune responses and open a new avenue to explore underlining mechanisms involved in the pathogenesis of ZIKV-associated diseases.

Alterations in deglutition in children with congenital Zika virus syndrome.

To characterize swallowing in children with congenital Zika virus syndrome in comparison to typical children. This cross-sectional study enrolled 45 children diagnosed with congenital Zika virus syndrome and 45 others with typical development. Swallowing was evaluated through clinical feeding evaluations Protocolo de Avaliação Clínica da Disfagia Pediátrica and using acoustic swallowing parameters (Doppler sonar). The mean age of children with congenital Zika virus syndrome was 26.69 ± 4.46 months and the mean head circumference was 29.20 ± 1.98 cm. Moderate/severe oropharyngeal dysphagia was found in 32(71.1%) of the children with congenital Zika virus syndrome. Significant differences were found between the groups on clinical evaluation: Children with congenital Zika virus syndrome presented insufficient lip closure 42(93.3%) and altered tonus of the tongue 35(77.8%) and cheeks 34(75.6%). In the children in the comparison group, only 6(13.3%) presented insufficient lip closure and 1(2.2%) had inadequate tongue posture. Changes during swallowing with liquid and spoonable food were not observed in the comparison group. When liquid/food was offered, affected children presented difficulties in sipping movements 14(77.8%) and lip/spoon contact 35(75%). The presence of residual food in the oral cavity after swallowing 38(86.4%) and clinical signs indicative of laryngotracheal penetration/aspiration, such as coughing, gagging and/or labored breathing, were also notable. No differences were found between the groups with regard to the acoustic parameters evaluated instrumentally. Children with congenital Zika virus syndrome present alterations in the oral phase of swallowing, as well as clinical signs indicative of pharyngeal phase impairment.

Fetuses and infants with Amyoplasia congenita in congenital Zika syndrome: The evidence of a viral cause. A narrative review of 144 cases.

Amyoplasia congenita is the most frequent type of arthrogryposis causing fetal hypokinesia, leading to congenital contractures at birth. The pathogenesis is thought to be impaired blood circulation to the fetus early in pregnancy, with hypotension and hypoxia damaging the anterior horn cells. In animal studies however a prenatal infection with a poliomyelitis-like viral agent was demonstrated. Congenital Zika virus syndrome (CZVS) has recently been described in infants with severe microcephaly, and in 10-25% of cases arthrogryposis. A search in PubMed for CZVS yielded 124 studies. After a selection for arthrogryposis, 35 papers were included, describing 144 cases. The studies were divided into two categories. 1) Those (87 cases) focussing on imaging or histological data of congenital brain defects, contained insufficient information to link arthrogryposis specifically to lesions of the brain or spinal motor neuron. 2) In the other 57 cases detailed clinical data could be linked to neurophysiological, imaging or histological data. In category 1 the most frequent brain abnormalities in imaging studies were ventriculomegaly, calcifications (subcortical, basal ganglia, cerebellum), hypoplasia of the brainstem and cerebellum, atrophy of the cerebral cortex, migration disorders and corpus callosum anomalies. In category 2, in 38 of 57 cases clinical data were indicative of Amyoplasia congenita. This diagnosis was confirmed by electromyographic findings (13 cases), by MRI (37 cases) or histology (12 cases) of the spinal cord. The latter showed small or absent lateral corticospinal tracts, and cell loss and degeneration of motor neuron cells. Zika virus-proteins and flavivirus-like particles were detected in cytoplasm of spinal neurons. The phenotype of arthrogryposis in CZVS is consistent with Amyoplasia congenita. These findings warrant search for an intrauterine infection with any neurotropic viral agent with affinity to spinal motor neurons in neonates with Amyoplasia.

Health care network for children with zika virus from the perspective of professionals.

To know the perspective of health professionals working in specialized care regarding the assistance offered to children with Congenital Zika Virus Syndrome in the Health Care Network. Qualitative study carried out in Campo Grande-MS through semi-structured interviews, between September and October 2020, with 12 professionals working in a reference service for people with physical and intellectual disabilities. Minayo's thematic analysis and the theoretical subsidies of the care model for chronic conditions were used for interpretation. Assistance in the network is weakened by aspects related to access, monitoring and integration between different professionals/services. The potential involves the implementation of the referral and counter-referral system, the communication/integration between these services and the training of professionals. The participants perceive that assistance is influenced by the availability of trained professionals to work in a network and the optimization of access and follow-up at different points of care.

Estressores e Coping materno no contexto da Síndrome Congênita do vírus Zika

Abstract Objective: Congenital Zika virus Syndrome is characterized by a series of neurological changes bearing consequences for child development. In view of the large number of children born with microcephaly and other neurological disorders, this qualitative study sought to understand and review the coping strategies used by 10 mothers of children affected by the syndrome. Methods: A semi-structured interview was applied, which identified four main maternal stressors: diagnosis; childcare routine; child treatment; and development and access to health services. Results: The most used coping strategies with regard to these stressors were: information-seeking, problem-solving, and delegation. Conclusion: The implications of such results for the care of this population are discussed within the perspective of expanding the adaptive coping to these stressors and ensuring the necessary support for those families in the long and difficult process of taking care of a child with this syndrome.

CONGENITAL ZIKA VIRUS SYNDROME-RELATED ANOMALIES DETECTED OVER THE SEVEN-YEAR HISTORY OF THE EPIDEMIC: A LITERATURE REVIEW

Background: In 2015, an alarming increase in microcephaly was recorded in Brazil, being associated to Zika virus (ZV) epidemic. The teratogenic effects of ZV, however, are not restricted to microcephaly only. Aim: To describe the body structures affected by the teratogenic potential of Zika virus congenital syndrome (ZVCS), in order to provide an overview of the anomalies detected and make this knowledge available to health professionals and to the scientific community. Methods: A narrative review was carried out between June 2020 and January 2022 in Portal de Periódicos CAPES, MEDLINE, Scopus, LILACS and SciELO databases. Scientific publications that addressed fetal organic structures that were affected by the teratogenic effects of ZVCS were included. Results: Thirty-two studies were included in this review and identified anomalies in cranium, orofacial structures, nervous system, joints, visual pathway and thoracic viscera. Conclusion: The teratogenic effects of ZVCS affect a broad spectrum of body structures. The children affected by ZVCS still require multidisciplinary health approach, so the present study is a helpful source of information for such professionals.

Splicing factor SF3B3, a NS5-binding protein, restricts ZIKV infection by targeting GCH1

Zika virus (ZIKV), a positive-sense single-stranded RNA virus, causes congenital ZIKV syndrome in children and Guillain-Barré Syndrome (GBS) in adults. ZIKV expresses nonstructural protein 5 (NS5), a large protein that is essential for viral replication. ZIKV NS5 confers the ability to evade interferon (IFN) signalling; however, the exact mechanism remains unclear. In this study, we employed affinity pull-down and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses and found that splicing factor 3b subunit 3 (SF3B3) is associated with the NS5-Flag pull-down complex through interaction with NS5. Functional assays showed that SF3B3 overexpression inhibited ZIKV replication by promoting IFN-stimulated gene (ISG) expression whereas silencing of SF3B3 inhibited expression of ISGs to promote ZIKV replication. GTP cyclohydrolase I (GCH1) is the first and rate-limiting enzyme in tetrahydrobiopterin (BH4) biosynthesis. NS5 upregulates the expression of GCH1 during ZIKV infection. And GCH1 marginally promoted ZIKV replication via the IFN pathway. Additionally, GCH1 expression is related to the regulation of SF3B3. Overexpression of the SF3B3 protein effectively reduced GCH1 protein levels, whereas SF3B3 knockdown increased its levels. These findings indicated that ZIKV NS5 binding protein SF3B3 contributed to the host immune response against ZIKV replication by modulating the expression of GCH1.