Search Results (141)

Background/Objectives: The Zika virus (ZIKV) represents an ongoing threat to public health due to its neurological and congenital complications. Even after 10 years since the first major outbreak, correlated with an increase in congenital ZIKV syndrome, there is still no vaccine or treatment for this infection. Among the various existing platforms, DNA vaccines combined with the use of immunoinformatics tools allow for the efficient selection of immunogenic epitopes and immunostimulatory molecules with greater flexibility, in addition to being simple to manufacture and having a higher cost–benefit ratio in production. Methods: In this work, we conducted an integrated approach, combining in silico analyses and in vivo experimental validations, for the development of multi-epitope DNA vaccines against ZIKV. The computational analyses confirmed structural stability, adequate solubility, absence of toxicity, and immune induction potential for constructs based on epitopes from the Envelope (E) and NS1 proteins. Therefore, we evaluated DNA constructs containing the ENV + NS1 epitopes, both with and without fusion to the ssPGIP signal peptide, in BALB/c mice. Results: Both vaccines increased the population of CD4⁺ and CD8⁺ T lymphocytes, in addition to the production of IgG antibodies associated with the Th1 profile. The fusion with ssPGIP broadened the response, stimulating the release of Th1, Th2, and Th17 cytokines, as well as enhancing antibody formation. In contrast, its absence was associated with a slight increase in CD4⁺ and CD8⁺ T cells, accompanied by restricted cytokine production. Conclusions: These results indicate that epitope-targeted techniques offer a viable and safe method for inducing robust immune responses, demonstrating that combining immunoinformatics methods with early preclinical testing is an effective strategy for ZIKV vaccine development. Furthermore, although the present study focused on initial immunogenic characterization, future studies involving viral challenge in a suitable animal model will be essential to conclusively determine the protective efficacy of these vaccine candidates. Full article

Zika virus (ZIKV) was first identified in Africa in the mid-20th century and circulated for decades with limited and often unnoticed human cases. This situation changed with the emergence of the Asian lineage, responsible for large outbreaks in the Pacific and the Americas and for severe complications such as Guillain–Barré syndrome and Congenital Zika Syndrome (CZS). In contrast, the African lineage, although frequently more efficient in replication, cytopathogenicity, and mosquito transmission in experimental systems, has not been linked to comparable epidemics or congenital disease clusters. This review summarizes current knowledge on the differences between African and Asian lineages at the molecular, cellular, and epidemiological levels. It highlights how genetic variation interacts with host immunity, ecological factors, and human activity to shape epidemic potential. Understanding these interactions is essential for anticipating future outbreaks and for improving strategies to mitigate the impact of emerging arboviruses. Full article

Children with Congenital Zika Virus Syndrome (CZVS) experience severe neurological and nutritional impairments. Although immediate clinical consequences are well-documented, long-term anthropometric and nutritional outcomes remain poorly understood. This study assessed longitudinal anthropometric and nutritional outcomes in children affected by CZVS. A cohort of 38 children aged ≥ 5 years diagnosed with CZVS was followed at a reference center in Northeast Brazil. Anthropometric measures (weight, height, BMI, head circumference) were collected using standardized methods, including digital scales and anthropometric tape measures. Growth was analyzed using WHO Anthro and WHO Anthro Plus software (version 3.2.2). Dietary intake was evaluated through two 24 h recalls and analyzed with NutWIN 2.5 software. Nutritional status was classified using WHO growth standards, and associations between dietary intake and BMI were statistically examined. Children showed significant linear growth improvement (p = 0.007) without corresponding weight gain, leading to worsening BMI classifications (p = 0.017). Dietary evaluations revealed limited dietary diversity, frequent intake of ultra-processed foods, inadequate fruit consumption, and widespread insufficiencies in caloric and micronutrient intake (zinc, calcium, iron, vitamin D). Low carbohydrate intake was significantly associated with inadequate BMI (p = 0.030). Multidisciplinary nutritional interventions addressing medical, dietary, educational, and socioeconomic factors are essential for improving health outcomes in children with CZVS. Full article

Zika virus (ZIKV) remains a pressing global health concern due to its association with congenital Zika syndrome and the current lack of approved antiviral therapies. In this study, we evaluated the antiviral activity of three novel thiazolidinedione derivatives, GQ-402, GQ-396, and ZKC-10, against ZIKV in vitro and investigated their potential molecular targets through in silico analysis. GQ-402 exhibited the highest antiviral potency, with an IC₅₀ of 15.7 µM, while ZKC-10 achieved the most substantial reduction in viral RNA levels, as determined by RT-qPCR. Molecular docking studies identified GQ-396 as the top-ranked inhibitor of the NS2B-NS3 protease and NS5 RNA-dependent RNA polymerase, suggesting distinct mechanisms of action among the compounds. These findings highlight the therapeutic potential of thiazolidinedione derivatives and underscore the need for further investigation to develop effective treatments for ZIKV infection. Full article

Background/Objectives: Congenital microcephaly is a clinical manifestation with a heterogeneous etiology, and its epidemiological surveillance relies on the systematic identification of cases and investigation of their underlying causes to inform preventive strategies and improve prognostic assessments. In Latin America, despite the existence of congenital anomaly reporting programs since 1967, the surveillance of microcephaly only gained substantial attention following the Zika virus (ZIKV) epidemic in 2015. Since then, efforts have predominantly concentrated on cases of infectious origin, often at the expense of recognizing endogenous etiologies, particularly those of genetic nature. This review aims to examine the role of genetic alterations in microcephaly pathogenesis and evaluates the limitations of current surveillance systems. Methods: A literature review centered on syndromic and non-syndromic genetic etiologies, alongside an analysis of Latin American surveillance frameworks (ECLAMC, RyVEMCE, ICBDSR, ReLAMC) was performed. Results: The findings reveal improved case detection and increased reported prevalence; however, the proportion of genetically attributed cases has remained stable. No systematic studies were found identifying the most common genetic causes; instead, genetic investigations were limited to isolated cases with a family history. Conclusions: While epidemiological surveillance systems in Latin America have advanced in the reporting of congenital microcephaly cases, substantial gaps remain in case ascertainment and etiological investigation, particularly concerning genetic contributions Full article

Zika virus (ZIKV) infection during pregnancy can cause a broad range of neurological birth defects, collectively named Congenital Zika Syndrome (CZS). We have previously shown that infection with the Puerto Rican isolate PRVABC59 (ZIKV-PR) results in abnormal oxygen transport in the placenta due to villous damage and uterine vasculitis in a nonhuman primate model. To investigate whether this type of damage occurs with endemically circulating strains in Thailand, we investigated a CZS case isolate, MU1-2017 (ZIKV-TH), in pregnant rhesus macaques. Pregnant animals (n = 3 per group) were infected subcutaneously with either ZIKV-PR or ZIKV-TH at ~50 days gestation (GD) and monitored for 40 days post-infection (GD90). Similar courses of viremia and immune activation were observed for both viruses when compared to uninfected controls. In addition, both viruses induced changes to the placental architecture, including spiral artery remodeling and the development of infarctions. Similar levels of viral RNA were detected at necropsy in maternal and fetal tissues. Overall, our results show that the ZIKV-TH strain MU1-2017 behaves similarly to the ZIKV-PR strain, and, importantly, provide evidence of in-utero infection with an additional contemporary strain of ZIKV. Full article

Background: The Zika virus (ZIKV) is an arbovirus linked to “Congenital Zika Syndrome” and a range of neurodevelopmental disorders (NDDs), with microcephaly as the most severe manifestation. Milder NDDs, such as autism spectrum disorders and delays in neuropsychomotor and language development, often go unnoticed in neonates, resulting in long-term social and academic difficulties. Murine models of ZIKV infection can be used to mimic part of the spectrum of motor and cognitive deficits observed in humans. These can be evaluated through behavioral tests, enabling comparison with gene expression profiles and aiding in the characterization of ZIKV-induced NDDs. Objectives: This study aimed to identify genes associated with behavioral changes following a subtle ZIKV infection in juvenile BALB/c mice. Methods: Neonatal mice were subcutaneously inoculated with ZIKV (MH544701.2) on postnatal day 1 (DPN) at a dose of 6.8 × 10³ PFU. Viral presence in the cerebellum and cortex was quantified at 10- and 30-days post-infection (DPI) using RT-qPCR. Neurobehavioral deficits were assessed at 30 DPI through T-maze, rotarod, and open field tests. Next-Generation Sequencing (NGS) was performed to identify differentially expressed genes (DEGs), which were analyzed through Gene Ontology (GO) and KEGG enrichment. Gene interaction networks were then constructed to explore gene interactions in the most enriched biological categories. Results: A ZIKV infection model was successfully established, enabling brain infection while allowing survival beyond 30 DPI. The infection induced mild cognitive behavioral changes, though motor and motivational functions remained unaffected. These cognitive changes were linked to the functional repression of synaptic vesicles and alterations in neuronal structure, suggesting potential disruptions in neuronal plasticity. Conclusions: Moderate ZIKV infection with circulating strains from the 2016 epidemic may cause dysregulation of genes related to immune response, alterations in cytoskeletal organization, and modifications in cellular transport mediated by vesicles. Despite viral control, neurocognitive effects persisted, including memory deficits and anxiety-like behaviors, highlighting the long-term neurological consequences of ZIKV infection in models that show no apparent malformations. Full article

Oropouche fever is caused by the Oropouche virus (OROV; Bunyaviridae, Orthobunyavirus), one of the most frequent arboviruses that infect humans in the Brazilian Amazon. This year, an OROV outbreak was identified in Brazil, and its vertical transmission was reported, which was associated with fetal death and microcephaly. We describe the clinical manifestations identified in three cases of congenital OROV infection with confirmed serology (OROV-IgM) in the mother-newborn binomial. One of the newborns died, and post-mortem molecular analysis using real-time RT-qPCR identified the OROV genome in several tissues. All three newborns were born in the Amazon region in Brazil, and the mothers reported fever, rash, headache, myalgia, and/or retro-orbital pain during pregnancy. The newborns presented with severe microcephaly secondary to brain damage and arthrogryposis, suggestive of an embryo/fetal disruptive process at birth. Brain and spinal images identified overlapping sutures, cerebral atrophy, brain cysts, thinning of the spinal cord, corpus callosum, and posterior fossa abnormalities. Fundoscopic findings included macular chorioretinal scars, focal pigment mottling, and vascular attenuation. The clinical presentation of vertical OROV infection resembled congenital Zika syndrome to some extent but presents some distinctive features on brain imaging and in several aspects of its neurological presentation. A recognizable syndrome with severe brain damage, neurological alterations, arthrogryposis, and fundoscopic abnormalities can be associated with in utero OROV infection. Full article

Zika virus (ZIKV) is a mosquito-borne flavivirus of the family Flaviviridae. The association between ZIKV and microcephaly was first described in Brazil in 2015. The risk of vertical transmission occurs in pregnant women with or without symptoms, and the risk of malformation appears to be worse when infection occurs in the first and second trimesters of pregnancy. The rate of vertical transmission varies from 26 to 65%, and not all fetuses develop malformations. The incidence of malformations resulting from transmission is uncertain, ranging from 6–8% in the US to 40% in Brazil. Congenital ZIKV syndrome is a set of clinical manifestations that can affect the fetus of a mother infected with ZIKV. The manifestations are broad and nonspecific, including microcephaly, subcortical calcifications, ocular changes, congenital contractures, early hypertension, and pyramidal and extrapyramidal signs. Other findings such as growth restriction and fetal miscarriage/death may also occur. Our aim in this article is to review the literature on mosquito transmission, clinical presentation, serologic diagnosis, intrauterine transmission, pre- and postnatal imaging diagnostic findings, and short- and long-term follow-up. Full article

Background/Objectives: Zika fever is a disease caused by the Zika virus (ZIKV). Symptomatic cases may be associated with neurological disorders in adults, as well as congenital Zika syndrome and other birth defects during pregnancy. In 2016, Zika fever was considered a public health problem by the World Health Organization (WHO), highlighting the need to develop new therapies against the disease. Currently, there is no antiviral or vaccine available to treat or prevent severe cases. Due to the lack of available therapeutics and few promising hit molecules, we computationally screened the well-described ZIKV protease (NS3^pro) as a drug target to revisit the small-molecule database Brazilian Compound Library (BraCoLi) and select potential inhibitors. Methods: We employed a consensus docking screening of a library of 1176 compounds using GOLD and DockThor. We selected 28 hits based on predicted binding affinity, and only the remnants of three compounds were available in the library at the time of this study for experimental validation. The hits were evaluated for their cytotoxic (CC₅₀) and effective concentrations (EC₅₀) for their potential antiviral activity in Vero cells. Results: The three hit compounds presented modest CC₅₀ values of 89.15 ± 3.72, >100, and 29.67 ± 1.01 μM, with the latter, a carbohydrate derivative, having an EC₅₀ value of >12.5 μM (~40% inhibition) against ZIKV PE243. Additionally, the essentially non-toxic compound, an arylfuran derivative, also inhibited the ZIKV NS3^pro with an IC₅₀ value of 17 μM but presented evidence of acting through a promiscuous mechanism for enzyme inhibition. Conclusion: This study highlights the relevance of revisiting existing small-molecule assets to identify novel therapeutic starting points against ZIKV, aiming for potential lead candidates in the future. Full article

This retrospective cohort study analyzed 7870 pregnant women, including 2269 with confirmed Zika virus (ZIKV) infection and 5601 without Zika infection, along with their fetuses and newborns. Data were sourced from multiple databases in the state of Rio de Janeiro, Brazil. A propensity score model was employed to control confounding factors and stratify outcomes by pregnancy trimester. Among ZIKV+ pregnant women, 49 cases of congenital microcephaly or congenital nervous system (CNS) abnormalities were identified (2.16%, or 193.9 cases in 10,000 live births), whereas 44 cases were identified among ZIKV− women (0.78%, or 71.4 cases in 10,000 live births). Multivariable analysis yielded an odds ratio of 2.46 (95% CI 1.30–4.64) overall, with 4.29 (95% CI 1.93–9.53) in the first trimester, 5.29 (95% CI 1.08–25.95) in the second trimester, and 0.68 (95% CI 0.21–2.14) in the third trimester. The most frequent findings among ZIKV+ cases included intracranial calcifications, ventriculomegaly, posterior fossa malformations, reduced brain volume, corpus callosum malformations, cortex dysplasia, lissencephaly, and pachygyria. Ophthalmologic abnormalities were detected in 55.5% of cases, and brainstem auditory evoked potential anomalies were reported in 33.3%. ZIKV infection can result in structural or functional anomalies. Given the absence of specific treatment for congenital Zika syndrome (CZS), clinical care should prioritize monitoring and managing neurological, motor, auditory, visual, and orthopedic disorders in all children with in utero ZIKV exposure, especially during the first and second trimesters of pregnancy. Full article

Background: In this study, we investigated the role of extracellular vesicles (EVs) in the pathogenesis of Congenital Zika Syndrome (CZS). Previous studies have highlighted the role of EVs in intercellular communication and the modulation of biological processes during viral infections, motivating our in-depth analysis. Our objective was to identify specific molecular signatures in the EVs of patients with CZS, focusing on their potential as biomarkers and on cellular pathways affected by the infection. Methods: We conducted advanced proteomic and metabolomic analyses using mass spectrometry for protein and metabolite identification. EVs were isolated from CZS patient samples and control groups using Izon qEV size-exclusion chromatography columns. Results: The analyzed EVs presented distinct molecular profiles in patients with CZS. Proteomic analysis revealed significant alterations in specific proteins, suggesting involvement in the PI3K-AKT-mTOR pathway, while metabolomics highlighted metabolites related to critical processes in Zika virus pathogenesis. These findings suggest a key role for the PI3K-AKT-mTOR pathway in regulating cellular processes during infection and indicate the involvement of EVs in intercellular communication. Additionally, the results identified potential biomarkers capable of aiding early diagnosis and assessing disease progression. Conclusions: This study demonstrates that EVs play a crucial role in intercellular communication during Zika virus infection. The identification of specific alterations in the PI3K-AKT-mTOR pathway highlights a possible therapeutic target, providing new opportunities for the development of more effective treatment strategies for CZS. Our findings significantly advance the understanding of CZS and underscore the need for further investigations using advanced techniques to validate and explore these potential molecular targets. Full article

Flaviviruses pose a major public health concern across the globe. Among them, Zika virus (ZIKV) is an emerging and reemerging arthropod-borne flavivirus that has become a major international public health problem following multiple large outbreaks over the past two decades. The majority of infections caused by ZIKV exhibit mild symptoms. However, the virus has been found to be associated with a variety of congenital neural abnormalities, including microcephaly in children and Guillain–Barre syndrome in adults. The exact prediction of the potential of ZIKV transmission is still enigmatic and underlines the significance of routine detection of the virus in suspected areas. ZIKV transmission from mother to fetus (including fetal abnormalities), viral presence in immune-privileged areas, and sexual transmission demonstrate the challenges in understanding the factors governing viral persistence and pathogenesis. This review illustrates the transmission patterns, epidemiology, control strategies (through vaccines, antivirals, and vectors), oncolytic aspects, molecular insights into neuro-immunopathogenesis, and other neuropathies caused by ZIKV. Additionally, we summarize in vivo and in vitro models that could provide an important platform to study ZIKV pathogenesis and the underlying governing cellular and molecular mechanisms. Full article

Zika virus (ZIKV), a mosquito-borne flavivirus, is a significant global health concern due to its association with neurodevelopmental disorders such as congenital Zika syndrome (CZS). This study aimed to compare the replication kinetics, viral persistence, cytopathogenic effects, and immune gene expression in human microglia cells (CHME-3) infected with an Asian lineage ZIKV (PRVABC59, referred to as ZIKV-PRV) and an African lineage ZIKV (IBH30656, referred to as ZIKV-IBH). We found that ZIKV-PRV replicated more efficiently and persisted longer while inducing lower levels of cell death and inflammatory gene activation compared with ZIKV-IBH. These findings suggest that the enhanced replication and persistence of ZIKV-PRV, along with its ability to evade innate immune responses, may underlie its increased neuropathogenic potential, especially in the context of CZS. In contrast, ZIKV-IBH, with its stronger immune gene activation and higher cytopathogenicity, may lead to more acute infections with faster viral clearance, thereby reducing the likelihood of chronic central nervous system (CNS) infection. This study provides crucial insights into the molecular and cellular mechanisms driving the differential pathogenicity of ZIKV lineages and highlights the need for further research to pinpoint the viral factors responsible for these distinct clinical outcomes. Full article