RESUMEN
The Zika virus (ZIKV) epidemic declared in Brazil between 2015 and 2016 was associated with an increased prevalence of severe congenital malformations, including microcephaly. The distribution of microcephaly cases was not uniform across the country, with a disproportionately higher incidence in the Northeast region (NE). Our previous work demonstrated that saxitoxin (STX), a toxin present in the drinking water reservoirs of the NE, exacerbated the damaging effects of ZIKV on the developing brain. We hypothesized that the impact of STX might vary among different neural cell types. While ZIKV infection caused severe damages on astrocytes and neural stem cells (NSCs), the addition of STX did not exacerbate these effects. We observed that neurons subjected to STX exposure were more prone to apoptosis and displayed higher ZIKV infection rate. These findings suggest that STX exacerbates the harmful effects of ZIKV on neurons, thereby providing a plausible explanation for the heightened severity of ZIKV-induced congenital malformations observed in Brazil's NE. This study highlights the importance of understanding the interactive effects of environmental toxins and infectious pathogens on neural development, with potential implications for public health policies.
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Astrocitos , Células-Madre Neurales , Neuronas , Saxitoxina , Infección por el Virus Zika , Virus Zika , Células-Madre Neurales/virología , Células-Madre Neurales/efectos de los fármacos , Células-Madre Neurales/metabolismo , Humanos , Virus Zika/fisiología , Astrocitos/virología , Astrocitos/efectos de los fármacos , Astrocitos/metabolismo , Neuronas/virología , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Infección por el Virus Zika/virología , Infección por el Virus Zika/patología , Saxitoxina/toxicidad , Apoptosis/efectos de los fármacos , Microcefalia/virología , Muerte Celular/efectos de los fármacos , Brasil , Células CultivadasRESUMEN
Aedes mosquito-borne viruses (ABVs) place a substantial strain on public health resources in the Americas. Vector control of Aedes mosquitoes is an important public health strategy to decrease or prevent spread of ABVs. The ongoing Targeted Indoor Residual Spraying (TIRS) trial is an NIH-sponsored clinical trial to study the efficacy of a novel, proactive vector control technique to prevent dengue virus (DENV), Zika virus (ZIKV), and chikungunya virus (CHIKV) infections in the endemic city of Merida, Yucatan, Mexico. The primary outcome of the trial is laboratory-confirmed ABV infections in neighborhood clusters. Despite the difficulties caused by the COVID-19 pandemic, by early 2021 the TIRS trial completed enrollment of 4,792 children aged 2-15 years in 50 neighborhood clusters which were allocated to control or intervention arms via a covariate-constrained randomization algorithm. Here, we describe the makeup and ABV seroprevalence of participants and mosquito population characteristics in both arms before TIRS administration. Baseline surveys showed similar distribution of age, sex, and socio-economic factors between the arms. Serum samples from 1,399 children were tested by commercially available ELISAs for presence of anti-ABV antibodies. We found that 45.1% of children were seropositive for one or more flaviviruses and 24.0% were seropositive for CHIKV. Of the flavivirus-positive participants, most were positive for ZIKV-neutralizing antibodies by focus reduction neutralization testing which indicated a higher proportion of participants with previous ZIKV than DENV infections within the cohort. Both study arms had statistically similar seroprevalence for all viruses tested, similar socio-demographic compositions, similar levels of Ae. aegypti infestation, and similar observed mosquito susceptibility to insecticides. These findings describe a population with a high rate of previous exposure to ZIKV and lower titers of neutralizing antibodies against DENV serotypes, suggesting susceptibility to future outbreaks of flaviviruses is possible, but proactive vector control may mitigate these risks.
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Aedes , Dengue , Insecticidas , Control de Mosquitos , Mosquitos Vectores , Humanos , Niño , Aedes/virología , Animales , México/epidemiología , Adolescente , Preescolar , Femenino , Control de Mosquitos/métodos , Masculino , Mosquitos Vectores/virología , Dengue/epidemiología , Dengue/prevención & control , Dengue/virología , Estudios Seroepidemiológicos , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/prevención & control , Virus Zika/inmunología , Virus Zika/aislamiento & purificación , Fiebre Chikungunya/epidemiología , Fiebre Chikungunya/prevención & control , Virus del Dengue/inmunología , Virus del Dengue/aislamiento & purificación , Virus Chikungunya/inmunologíaRESUMEN
INTRODUCTION: Many studies have highlighted the use of oncolytic viruses as a new class of therapeutic agents for central nervous system (CNS) tumors, especially glioblastomas (GMB). Zika Virus (ZIKV) proteins targeted to specific stem cells have been studied in vitro and animal models with promising results. MATERIALS AND METHODS: A systematic review was evaluated the efficacy and safety of the ZIKV use for CNS tumors treatment. Data were extracted and the in vivo studies were evaluated using the Robins-I tool. We assessed bias in each study using criteria such as selection bias, performance bias, detection bias, attrition bias, reporting bias, and others. According to Cochrane guidelines, bias was classified as high, low, or uncertain. High bias occurred when studies did not meet the criteria. Low bias was assigned when criteria were clearly met. Uncertain bias reflected insufficient information for a clear classification. RESULTS: The 14 included studies shown that ZIKV reduced cell viability or inhibited the growth, proliferation of glioma stem cells (GSCs), and Bcl2 expression - which could potentially enhance the effect of chemotherapy/radiotherapy; caused cytopathic effects, induced tumor cell damage, manifested oncolytic properties, and even selectively safely killed GSCs; ultimately, it led to significant tumor remission and enhanced long-term survival through enhanced T-cell response. CONCLUSIONS: Although current evidence suggests ZIKV as a promising treatment for CNS tumors and may improve survival when combined with surgery and radiotherapy. Despite limited human evidence, it shows potential benefits. Further research is needed to confirm safety, efficacy, and optimize treatment in humans.
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Neoplasias Encefálicas , Viroterapia Oncolítica , Virus Zika , Animales , Humanos , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/virología , Proliferación Celular , Glioblastoma/terapia , Glioblastoma/virología , Células Madre Neoplásicas/virología , Viroterapia Oncolítica/métodos , Virus OncolíticosRESUMEN
Zika virus (ZIKV) is an arbovirus with maternal, sexual, and TORCH-related transmission capabilities. After 2015, Brazil had the highest number of ZIVK-infected pregnant women who lost their babies or delivered them with Congenital ZIKV Syndrome (CZS). ZIKV triggers an immune defense in the placenta. This immune response counts with the participation of interleukins and transcription factors. Additionally, it has the potential involvement of human endogenous retroviruses (HERVS). Interleukins are immune response regulators that aid immune tolerance and support syncytial structure development in the placenta, where syncytin receptors facilitate vital cell-to-cell fusion events. HERVs are remnants of ancient viral infections that integrate into the genome and produce syncytin proteins crucial for placental development. Since ZIKV can infect trophoblast cells, we analyzed the relationship between ZIKV infection, HERV, interleukin, and transcription factor modulations in the placenta. To investigate the impact of ZIKV on trophoblast cells, we examined two cell types (BeWo and HTR8) infected with ZIKV-MR766 (African) and ZIKV-IEC-Paraíba (Asian-Brazilian) using Taqman and RT2 Profiler PCR Array assays. Our results indicate that early ZIKV infection (24-72 h) does not induce differential interleukins, transcription factors, and HERV expression. However, we show that the expression of a few of these host defense genes appears to be linked independently of ZIKV infection. Future studies involving additional trophoblastic cell lineages and extended infection timelines will illuminate the dynamic interplay between ZIKV, HERVs, interleukins, and transcription factors in the placenta.
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Retrovirus Endógenos , Interleucinas , Factores de Transcripción , Trofoblastos , Infección por el Virus Zika , Virus Zika , Humanos , Trofoblastos/virología , Trofoblastos/metabolismo , Femenino , Infección por el Virus Zika/virología , Infección por el Virus Zika/genética , Retrovirus Endógenos/genética , Embarazo , Interleucinas/genética , Interleucinas/metabolismo , Factores de Transcripción/metabolismo , Factores de Transcripción/genética , Placenta/virología , Placenta/metabolismo , Línea CelularRESUMEN
In the current biopharmaceutical scenario, constant bioprocess monitoring is crucial for the quality and integrity of final products. Thus, process analytical techniques, such as those based on Raman spectroscopy, have been used as multiparameter tracking methods in pharma bioprocesses, which can be combined with chemometric tools, like Partial Least Squares (PLS) and Artificial Neural Networks (ANN). In some cases, applying spectra pre-processing techniques before modeling can improve the accuracy of chemometric model fittings to observed values. One of the biological applications of these techniques could have as a target the virus-like particles (VLP), a vaccine production platform for viral diseases. A disease that has drawn attention in recent years is Zika, with large-scale production sometimes challenging without an appropriate monitoring approach. This work aimed to define global models for Zika VLP upstream production monitoring with Raman considering different laser intensities (200 mW and 495 mW), sample clarification (with or without cells), spectra pre-processing approaches, and PLS and ANN modeling techniques. Six experiments were performed in a benchtop bioreactor to collect the Raman spectral and biochemical datasets for modeling calibration. The best models generated presented a mean absolute error and mean relative error respectively of 3.46 × 105 cell/mL and 35 % for viable cell density (Xv); 4.1 % and 5 % for cell viability (CV); 0.245 g/L and 3 % for glucose (Glc); 0.006 g/L and 18 % for lactate (Lac); 0.115 g/L and 26 % for glutamine (Gln); 0.132 g/L and 18 % for glutamate (Glu); 0.0029 g/L and 3 % for ammonium (NH4+); and 0.0103 g/L and 2 % for potassium (K+). Sample without conditioning (with cells) improved the models' adequacy, except for Glutamine. ANN better predicted CV, Gln, Glu, and K+, while Xv, Glc, Lac, and NH4+ presented no statistical difference between the chemometric tools. For most of the assessed experimental parameters, there was no statistical need for spectra pre-filtering, for which the models based on the raw spectra were selected as the best ones. Laser intensity impacts quality model predictions in some parameters, Xv, Gln, and K+ had a better performance with 200 mW of intensity (for PLS, ANN, and ANN, respectively), for CV the 495 mW laser intensity was better (for PLS), and for the other biochemical variables, the use of 200 or 495 mW did not impact model fitting adequacy.
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Espectrometría Raman , Virus Zika , Espectrometría Raman/métodos , Reactores Biológicos , Análisis de los Mínimos Cuadrados , Redes Neurales de la Computación , Rayos Láser , Humanos , Infección por el Virus Zika/virología , AnimalesRESUMEN
Zika virus (ZIKV) is an emergent flavivirus that represents a global public health concern due to its association with severe neurological disorders. NS2B is a multifunctional viral membrane protein primarily used to regulate viral protease activity and is crucial for virus replication, making it an appealing target for antiviral drugs. This study presents the structural elucidation of full-length ZIKV NS2B in sodium dodecyl sulfate (SDS) micelles using solution nuclear magnetic resonance experimental data and RosettaMP. The protein structure has four transmembrane α-helices, two amphipathic α-helices, and a ß-hairpin in the hydrophilic region. NS2B presented secondary and tertiary stability in different concentrations of SDS. Furthermore, we studied the dynamics of NS2B in SDS micelles through relaxation parameters and paramagnetic relaxation enhancement experiments. The findings were consistent with the structural calculations. Our work will be essential in understanding the role of NS2B in viral replication and screening for inhibitors against ZIKV.
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Proteínas no Estructurales Virales , Virus Zika , Virus Zika/efectos de los fármacos , Proteínas no Estructurales Virales/química , Proteínas no Estructurales Virales/metabolismo , Micelas , Espectroscopía de Resonancia Magnética , Simulación de Dinámica MolecularRESUMEN
OBJECTIVE: In this study, we have synthesized 19 Thiazolidine (TZD) derivatives to investigate their potential anti-ZIKV effects. METHODS: Nineteen thiazolidine derivatives were synthesized and evaluated for their cytotoxicity and antiviral activity against the ZIKA virus. RESULTS: Among them, six demonstrated remarkable selectivity against the ZIKV virus, exhibiting IC50 values of <5µM, and the other compounds did not demonstrate selectivity for the virus. Interestingly, several derivatives effectively suppressed the replication of ZIKV RNA copies, with derivatives significantly reducing ZIKV mRNA levels at 24 hours post-infection (hpi). Notably, two derivatives (ZKC-4 and -9) stood out by demonstrating a protective effect against ZIKV cell entry. Informed by computational analysis of binding affinity and intermolecular interactions within the NS5 domain's N-7 and O'2 positions, ZKC-4 and FT-39 displayed the highest predicted affinities. Intriguingly, ZKC-4 and ZKC-9 derivatives exhibited the most favorable predicted binding affinities for the ZIKV-E binding site. CONCLUSION: The significance of TZDs as potent antiviral agents is underscored by these findings, suggesting that exploring TZD derivatives holds promise for advancing antiviral therapeutic strategies.
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Antivirales , Tiazolidinas , Virus Zika , Antivirales/farmacología , Antivirales/química , Antivirales/síntesis química , Tiazolidinas/farmacología , Tiazolidinas/química , Tiazolidinas/síntesis química , Virus Zika/efectos de los fármacos , Humanos , Relación Estructura-Actividad , Estructura Molecular , Replicación Viral/efectos de los fármacos , Pruebas de Sensibilidad Microbiana , Relación Dosis-Respuesta a Droga , Animales , Chlorocebus aethiops , Células Vero , Simulación del Acoplamiento MolecularRESUMEN
Zika virus (ZIKV) infection was first reported in 2015 in Brazil as causing microcephaly and other developmental abnormalities in newborns, leading to the identification of Congenital Zika Syndrome (CZS). Viral infections have been considered an environmental risk factor for neurodevelopmental disorders outcome, such as Autism Spectrum Disorder (ASD). Moreover, not only the infection per se, but maternal immune system activation during pregnancy, has been linked to fetal neurodevelopmental disorders. To understand the impact of ZIKV vertical infection on brain development, we derived induced pluripotent stem cells (iPSC) from Brazilian children born with CZS, some of the patients also being diagnosed with ASD. Comparing iPSC-derived neurons from CZS with a control group, we found lower levels of pre- and postsynaptic proteins and reduced functional synapses by puncta co-localization. Furthermore, neurons and astrocytes derived from the CZS group showed decreased glutamate levels. Additionally, the CZS group exhibited elevated levels of cytokine production, one of which being IL-6, already associated with the ASD phenotype. These preliminary findings suggest that ZIKV vertical infection may cause long-lasting disruptions in brain development during fetal stages, even in the absence of the virus after birth. These disruptions could contribute to neurodevelopmental disorders manifestations such as ASD. Our study contributes with novel knowledge of the CZS outcomes and paves the way for clinical validation and the development of potential interventions to mitigate the impact of ZIKV vertical infection on neurodevelopment.
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Encéfalo , Células Madre Pluripotentes Inducidas , Transmisión Vertical de Enfermedad Infecciosa , Sinapsis , Infección por el Virus Zika , Virus Zika , Humanos , Infección por el Virus Zika/virología , Infección por el Virus Zika/patología , Femenino , Virus Zika/patogenicidad , Sinapsis/patología , Sinapsis/metabolismo , Encéfalo/virología , Encéfalo/patología , Embarazo , Células Madre Pluripotentes Inducidas/metabolismo , Células Madre Pluripotentes Inducidas/virología , Neuronas/virología , Neuronas/metabolismo , Neuronas/patología , Masculino , Astrocitos/virología , Astrocitos/metabolismo , Enfermedades Neuroinflamatorias/virología , Enfermedades Neuroinflamatorias/patología , Enfermedades Neuroinflamatorias/metabolismo , Complicaciones Infecciosas del Embarazo/virología , Complicaciones Infecciosas del Embarazo/patología , Brasil , Recién Nacido , Trastorno del Espectro Autista/virología , NiñoRESUMEN
Zika virus (ZIKV) infection in pregnancy is associated with severe abnormalities of the brain and eye and other adverse outcomes. Zika en Embarazadas y Niños was a prospective cohort study conducted in multiple Colombian cities that enrolled pregnant women in their first trimester. Specimens collected from pregnant women (n = 1,519) during February 2017-September 2018 and their infants (n = 1,080) during June 2017-March 2019 were tested for prenatal ZIKV infection by nucleic acid amplification tests or IgM antibody testing. Zika virus infection in pregnancy was present in 3.2% of pregnant women (incidence rate [IR] per 1,000 person-months = 5.9, 95% CI: 4.3-7.8). Presumptive ZIKV infection was present in 0.8% of infants (IR = 1.6, 95% CI: 0.7-2.9). Five percent of infants with prenatal ZIKV exposure or infection presented with Zika-associated abnormalities; 4.7% were small for gestational age. Understanding the risk of ZIKV infection during pregnancy and associated adverse outcomes can help inform counseling efforts.
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Dengue , Complicaciones Infecciosas del Embarazo , Infección por el Virus Zika , Humanos , Femenino , Embarazo , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/complicaciones , Colombia/epidemiología , Estudios Prospectivos , Complicaciones Infecciosas del Embarazo/epidemiología , Complicaciones Infecciosas del Embarazo/virología , Adulto , Dengue/epidemiología , Recién Nacido , Virus Zika/aislamiento & purificación , Adulto Joven , Adolescente , Resultado del Embarazo , Lactante , MasculinoRESUMEN
Maternal Zika virus (ZIKV) infection during pregnancy has been associated with severe intrauterine growth restriction (IUGR), placental damage, metabolism disturbances, and newborn neurological abnormalities. Here, we investigated the impact of maternal ZIKV infection on placental nutrient transporters and nutrient-sensitive pathways. Immunocompetent (C57BL/6) mice were injected with Low (103 PFU-ZIKVPE243) or High (5 × 107 PFU-ZIKVPE243) ZIKV titers at gestational day (GD) 12.5, and tissue was collected at GD18.5 (term). Fetal-placental growth was impaired in male fetuses, which exhibited higher placental expression of the ZIKV infective marker, eukaryotic translation initiation factor 2 (eIF2α), but lower levels of phospho-eIF2α. There were no differences in fetal-placental growth in female fetuses, which exhibited no significant alterations in placental ZIKV infective markers. Furthermore, ZIKV promoted increased expression of glucose transporter type 1 (Slc2a1/Glut1) and decreased levels of glucose-6-phosphate in female placentae, with no differences in amino acid transport potential. In contrast, ZIKV did not impact glucose transporters in male placentae but downregulated sodium-coupled neutral amino acid 2 (Snat2) transporter expression. We also observed sex-dependent differences in the hexosamine biosynthesis pathway (HBP) and O-GlcNAcylation in ZIKV-infected pregnancies, showing that ZIKV can disturb placental nutrient sensing. Our findings highlight molecular alterations in the placenta caused by maternal ZIKV infection, shedding light on nutrient transport, sensing, and availability. Our results also suggest that female and male placentae employ distinct coping mechanisms in response to ZIKV-induced metabolic changes, providing insights into therapeutic approaches for congenital Zika syndrome.
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Desarrollo Fetal , Ratones Endogámicos C57BL , Placenta , Transducción de Señal , Infección por el Virus Zika , Virus Zika , Animales , Femenino , Infección por el Virus Zika/metabolismo , Infección por el Virus Zika/virología , Embarazo , Ratones , Placenta/metabolismo , Placenta/virología , Masculino , Desarrollo Fetal/fisiología , Complicaciones Infecciosas del Embarazo/virología , Complicaciones Infecciosas del Embarazo/metabolismo , Nutrientes/metabolismo , Transportador de Glucosa de Tipo 1/metabolismoRESUMEN
The increase in incidence and geographical expansion of viruses transmitted by the Aedes mosquitoes, such as dengue (DENV) and zika (ZIKV) in the Americas, represents a burden for healthcare systems in tropical and subtropical regions. These and other under-detected arboviruses co-circulate in Costa Rica, adding additional complexity to their management due to their shared epidemiological behavior and similarity of symptoms in early stages. Since diagnostics of febrile illness is mostly based on clinical symptoms alone, we gathered acute-phase serum and urine from 399 samples of acute dengue-like cases from two healthcare facilities of Costa Rica, during an outbreak of arboviruses from July 2017 to May 2018, and tested them using molecular and serological methods. The analyses showed that of the clinically presumptive arbovirus cases that were reported, only 39.4% (n=153) of the samples were confirmed positive by RT-PCR to be DENV (DENV (10.3%), CHIKV (0.2%), ZIKV (27.3%), or mixed infections (1.5%). RT-PCR for other alphaviruses and flaviviruses, and PCR for Leptospira sp were negative. Furthermore, to assess flavivirus positivity in post-acute patients, the negative sera were tested against Dengue-IgM. 20% of sera were found positive, confounding even more the definitive number of cases, and emphasizing the need of several distinct diagnostic tools for accurate diagnostics. Molecular characterization of the prM and E genes from isolated viruses revealed that the American/Asian genotype of DENV-2 and the Asian lineage of ZIKV were circulating during this outbreak. Two different clades of DENV-2 American/Asian genotype were identified to co-circulate in the same region and a difference in the platelet and leukocyte count was noted between people infected with each clade, suggesting a putative distinct virulence. Our study sheds light on the necessity for healthcare strategies in managing arbovirus outbreaks, emphasizing the importance of comprehensive molecular and serological diagnostic approaches, as well as molecular characterization. This approach aids in enhancing our understanding of the clinical and epidemiological aspects of arboviral diseases during outbreaks. Our research highlights the need to strengthen training programs for health professionals and the need to increase research-based on laboratory evidence for diagnostic accuracy, guidance, development and implementation of public health interventions and epidemiological surveillance.
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Virus del Dengue , Dengue , Brotes de Enfermedades , Infección por el Virus Zika , Virus Zika , Humanos , Costa Rica/epidemiología , Dengue/epidemiología , Dengue/diagnóstico , Dengue/virología , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/diagnóstico , Infección por el Virus Zika/virología , Virus Zika/genética , Virus Zika/aislamiento & purificación , Virus del Dengue/genética , Virus del Dengue/aislamiento & purificación , Virus del Dengue/clasificación , Femenino , Masculino , Adulto , Adolescente , Persona de Mediana Edad , Adulto Joven , Niño , Preescolar , Anciano , Región del Caribe/epidemiología , Filogenia , Lactante , Animales , Coinfección/epidemiología , Coinfección/virología , Anciano de 80 o más Años , Anticuerpos Antivirales/sangreRESUMEN
AIM: Congenital Zika Virus Syndrome (CZS) presents notable hurdles to neurodevelopment, with language development emerging as a crucial aspect. This study investigates sleep patterns and language skills in children with CZS, aiming to explore the potential synchronization of sleep development with their neurodevelopment. METHOD: We studied cross-sectionally 135 children with CZS aged 0 to 48 months, investigating sleep using the BISQ Questionnaire. Language development was assessed using the Early Language Milestone Scale, while motor development and cognitive and social ability were assessed using the Bayley Scales of Infant and Young Child Development 3rd edition. We also studied longitudinally a cohort of 16 children (initially aged 0 to 12 months) whom we followed for four years, assessing at one-year intervals. RESULTS: Sleep disturbances and language deficits were highly frequent in this population. In the 0-12 months group, a late bedtime and frequent nighttime awakenings were associated with poorer auditory expressive skills. At 13-24 months, nighttime awakenings were associated with poorer auditory expressive skills, while among 25-36-month-olds decreased auditory receptive skills were associated with longer sleep onset latency and reduced nighttime sleep duration. CONCLUSION: The brain alterations caused by Zika virus infection affect both sleep disturbances and delays in language development. It is possible that sleep disturbance may be a mediating factor in the pathway between CZS and delayed language development, as the three analyzed language skills showed a correlation with sleep parameters.
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Desarrollo del Lenguaje , Sueño , Infección por el Virus Zika , Humanos , Infección por el Virus Zika/complicaciones , Infección por el Virus Zika/fisiopatología , Infección por el Virus Zika/virología , Infección por el Virus Zika/congénito , Lactante , Femenino , Masculino , Preescolar , Sueño/fisiología , Recién Nacido , Estudios Transversales , Trastornos del Sueño-Vigilia/fisiopatología , Trastornos del Sueño-Vigilia/virología , Virus Zika/fisiología , Estudios Longitudinales , Encuestas y Cuestionarios , Trastornos del Desarrollo del Lenguaje/fisiopatología , Trastornos del Desarrollo del Lenguaje/virologíaRESUMEN
Fragmented landscapes in Mexico, characterized by a mix of agricultural, urban, and native vegetation cover, presents unique ecological characteristics that shape the mosquito community composition and mosquito-borne diseases. The extent to which landscape influences mosquito populations and mosquito-borne diseases is still poorly understood. This work assessed the effect of landscape metrics -agriculture, urban, and native vegetation cover- on mosquito diversity and arbovirus presence in fragmented tropical deciduous forests in Central Mexico during 2021. Among the 21 mosquito species across six genera we identified, Culex quinquefasciatus was the most prevalent species, followed by Aedes aegypti, Ae. albopictus, and Ae. epactius. Notably, areas with denser native vegetation cover displayed higher mosquito species richness, which could have an impact on phenomena such as the dilution effect. Zika and dengue virus were detected in 85% of captured species, with first reports of DENV in several Aedes species and ZIKV in multiple Aedes and Culex species. These findings underscore the necessity of expanding arbovirus surveillance beyond Ae. aegypti and advocate for a deeper understanding of vector ecology in fragmented landscapes to adequately address public health strategies.
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Arbovirus , Biodiversidad , Culicidae , Mosquitos Vectores , Animales , Arbovirus/aislamiento & purificación , Arbovirus/clasificación , México/epidemiología , Mosquitos Vectores/virología , Mosquitos Vectores/clasificación , Culicidae/virología , Culicidae/clasificación , Agricultura , Aedes/virología , Aedes/clasificación , Ciudades , Virus Zika/aislamiento & purificación , Virus Zika/genética , EcosistemaRESUMEN
As part of an epidemiologic study of the Zika virus (ZIKV) in deer (Cervidae), samples from 56 captive deer in south and southeastern Brazil were tested for evidence of ZIKV. Three samples were positive using reverse-transcription quantitative PCR, although no samples were positive by virus isolation.
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Ciervos , Infección por el Virus Zika , Virus Zika , Animales , Brasil/epidemiología , Ciervos/virología , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/veterinaria , Infección por el Virus Zika/virología , Virus Zika/aislamiento & purificación , Femenino , Masculino , Animales de ZoológicoRESUMEN
In response to the 2015 Zika virus (ZIKV) epidemic that occurred in Brazil, numerous commercial serological assays have been developed for clinical and research applications. Diagnosis of recent infection in pregnant women remains challenging. Having standardized, comparative studies of ZIKV tests is important for implementing optimal diagnostic testing and disease surveillance. This is especially important for serology tests used to detect ZIKV infection given that antibodies against ZIKV can cross-react with other arboviruses in the same virus family, such as dengue virus (DENV), yellow fever virus (YFV) and West Nile virus (WNV). We looked at the sensitivity and specificity of tests detecting ZIKV antibodies (IgM, IgG) from multiple manufacturers using panels of samples previously collected with known exposure to ZIKV and other arboviruses. We found that performance of the IgM tests was highly variable, with only one test (Inbios 2.0 IgM capture ELISA) having both high sensitivity and specificity. All IgG tests showed good sensitivity; however, specificity was highly variable, with some assays giving false-positive results on samples infected by another flavivirus. Overall, the results confirmed that accurate ZIKV antibody testing is challenging, especially in specimens from regions endemic for multiple other flaviviruses, and highlight the importance of available and suitable reference samples to evaluate ZIKV diagnostics.
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Anticuerpos Antivirales , Inmunoglobulina G , Inmunoglobulina M , Sensibilidad y Especificidad , Pruebas Serológicas , Infección por el Virus Zika , Virus Zika , Humanos , Virus Zika/inmunología , Infección por el Virus Zika/diagnóstico , Infección por el Virus Zika/inmunología , Infección por el Virus Zika/sangre , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , Pruebas Serológicas/métodos , Pruebas Serológicas/normas , Inmunoglobulina M/sangre , Inmunoglobulina G/sangre , Ensayo de Inmunoadsorción Enzimática/métodos , Ensayo de Inmunoadsorción Enzimática/normas , Reacciones Cruzadas/inmunología , Femenino , Embarazo , BrasilRESUMEN
Arthropod-borne viruses represent a crucial public health threat. Current arboviral serology assays are either labor intensive or incapable of distinguishing closely related viruses, and many zoonotic arboviruses that may transition to humans lack any serologic assays. In this study, we present a programmable phage display platform, ArboScan, that evaluates antibody binding to overlapping peptides that represent the proteomes of 691 human and zoonotic arboviruses. We confirm that ArboScan provides detailed antibody binding information from animal sera, human sera, and an arthropod blood meal. ArboScan identifies distinguishing features of antibody responses based on exposure history in a Colombian cohort of Zika patients. Finally, ArboScan details epitope level information that rapidly identifies candidate epitopes with potential protective significance. ArboScan thus represents a resource for characterizing human and animal arbovirus antibody responses at cohort scale.
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Anticuerpos Antivirales , Arbovirus , Humanos , Arbovirus/inmunología , Arbovirus/aislamiento & purificación , Animales , Anticuerpos Antivirales/inmunología , Anticuerpos Antivirales/sangre , Péptidos/inmunología , Péptidos/química , Infección por el Virus Zika/virología , Infección por el Virus Zika/inmunología , Infección por el Virus Zika/sangre , Virus Zika/inmunología , Epítopos/inmunología , Pruebas Serológicas/métodos , Infecciones por Arbovirus/virología , Infecciones por Arbovirus/inmunología , Proteoma , Colombia , Femenino , Biblioteca de Péptidos , Técnicas de Visualización de Superficie Celular , MasculinoRESUMEN
BACKGROUND AND OBJECTIVES: In Brazil, urban arboviruses, such as dengue virus (DENV), Zika virus (ZIKV) and chikungunya virus (CHIKV), constitute a major public health problem, and due to their endemicity and asymptomatic cases, they pose a potential threat to blood donations. Rio de Janeiro (RJ), Brazil, has been impacted by extensive DENV epidemics over the last 30 years and, after 2015, by CHIKV and ZIKV. MATERIALS AND METHODS: Urban arboviruses DENV, ZIKV and CHIKV were investigated in blood donations (n = 778) at the State Institute of Hematology, HEMORIO (RJ) from 2019 to 2022 by serological and molecular methods. RESULTS: An overall arbovirus exposure was observed in 26.1% of the blood donations. Anti-DENV IgM was detected in 4.0% of samples and two donations were DENV NS1 positive. Positive anti-CHIKV IgM was observed in 4.7% of the donations. Co-detection of anti-CHIKV IgM and anti-DENV IgM was observed in 1.0% of donors, and CHIKV prevalence was 21.3%. All blood donations tested were negative for the DENV, ZIKV and CHIKV RNA. CONCLUSION: IgM seroprevalence to the arboviruses analyzed here is an indicator of recent infection in asymptomatic donors, showing that the population of blood donors can be a vehicle for new infections, especially during epidemic periods.
Asunto(s)
Donantes de Sangre , Virus del Dengue , Infección por el Virus Zika , Humanos , Donantes de Sangre/estadística & datos numéricos , Brasil/epidemiología , Femenino , Masculino , Adulto , Infección por el Virus Zika/epidemiología , Infección por el Virus Zika/sangre , Virus Zika , Inmunoglobulina M/sangre , Fiebre Chikungunya/epidemiología , Fiebre Chikungunya/sangre , Dengue/epidemiología , Dengue/sangre , Estudios Seroepidemiológicos , Anticuerpos Antivirales/sangre , Enfermedades Endémicas , Persona de Mediana Edad , Infecciones por Arbovirus/epidemiología , Infecciones por Arbovirus/sangre , Arbovirus , Virus Chikungunya , Adolescente , Adulto Joven , Donación de SangreRESUMEN
BACKGROUND: Peptide drugs are advantageous because they are subject to rational design and exhibit highly diverse structures and broad biological activities. The NS2B-NS3 protein is a particularly promising flavivirus therapeutic target, with extensive research on the development of inhibitors as therapeutic candidates, and was used as a model in this work to determine the mechanism by which GA-Hecate inhibits ZIKV replication. OBJECTIVE: The present study aimed to evaluate the potential of GA-Hecate, a new antiviral developed by our group, against the Brazilian Zika virus and to evaluate the mechanism of action of this compound on the flavivirus NS2B-NS3 protein. METHODS: Solid-phase peptide Synthesis, High-Performance Liquid Chromatography, and Mass Spectrometry were used to obtain, purify, and characterize the synthesized compound. Real-time and enzymatic assays were used to determine the antiviral potential of GA-Hecate against ZIKV. RESULTS: The RT-qPCR results showed that GA-Hecate decreased the number of ZIKV RNA copies in the virucidal, pre-treatment, and post-entry assays, with 5- to 6-fold fewer RNA copies at the higher nontoxic concentration in Vero cells (HNTC: 10 µM) than in the control cells. Enzymatic and kinetic assays indicated that GA-Hecate acts as a competitive ZIKV NS2B-NS3 protease inhibitor with an IC50 of 32 nM and has activity against the yellow fever virus protease. CONCLUSION: The results highlight the antiviral potential of the GA-Hecate bioconjugate and open the door for the development of new antivirals.
Asunto(s)
Antivirales , Proteínas no Estructurales Virales , Replicación Viral , Virus Zika , Virus Zika/efectos de los fármacos , Antivirales/farmacología , Antivirales/química , Proteínas no Estructurales Virales/metabolismo , Proteínas no Estructurales Virales/antagonistas & inhibidores , Animales , Chlorocebus aethiops , Células Vero , Replicación Viral/efectos de los fármacos , Serina Endopeptidasas/metabolismo , Péptidos/farmacología , Péptidos/química , ARN Helicasas/metabolismo , ARN Helicasas/antagonistas & inhibidores , Infección por el Virus Zika/tratamiento farmacológico , Infección por el Virus Zika/virología , Humanos , Inhibidores de Proteasas/farmacología , Inhibidores de Proteasas/química , Proteasas Virales , Nucleósido-Trifosfatasa , ARN Helicasas DEAD-boxRESUMEN
Monocytes are the primary targets of Zika virus (ZIKV) and are associated with ZIKV pathogenesis. Currently, there is no effective treatment for ZIKV infection. It is known that 1,25-dihydroxy vitamin D3 (VitD3) has strong antiviral activity in dengue virus-infected macrophages, but it is unknown whether VitD3 inhibits ZIKV infection in monocytes. We investigated the relationship between ZIKV infection and the expression of genes of the VitD3 pathway, as well as the inflammatory response of infected monocytes in vitro. ZIKV replication was evaluated using a plaque assay, and VitD3 pathway gene expression was analyzed by RT-qPCR. Pro-inflammatory cytokines/chemokines were quantified using ELISA. We found that VitD3 did not suppress ZIKV replication. The results showed a significant decrease in the expression of vitamin D3 receptor (VDR), cytochrome P450 family 24 subfamily A member 1 (CYP24A1), and cathelicidin antimicrobial peptide (CAMP) genes upon ZIKV infection. Treatment with VitD3 was unable to down-modulate production of pro-inflammatory cytokines, except TNF-α, and chemokines. This suggests that ZIKV infection inhibits the expression of VitD3 pathway genes, thereby preventing VitD3-dependent inhibition of viral replication and the inflammatory response. This is the first study to examine the effects of VitD3 in the context of ZIKV infection, and it has important implications for the role of VitD3 in the control of viral replication and inflammatory responses during monocyte infection.
Asunto(s)
Catelicidinas , Monocitos , Replicación Viral , Vitamina D3 24-Hidroxilasa , Infección por el Virus Zika , Virus Zika , Humanos , Péptidos Catiónicos Antimicrobianos/metabolismo , Péptidos Catiónicos Antimicrobianos/farmacología , Citocinas/metabolismo , Citocinas/genética , Monocitos/virología , Monocitos/metabolismo , Monocitos/inmunología , Receptores de Calcitriol/metabolismo , Receptores de Calcitriol/genética , Replicación Viral/efectos de los fármacos , Vitamina D3 24-Hidroxilasa/genética , Vitamina D3 24-Hidroxilasa/metabolismo , Virus Zika/fisiología , Infección por el Virus Zika/virología , Infección por el Virus Zika/metabolismoRESUMEN
Zika virus (ZIKV) is an emerging mosquito-borne flavivirus that causes severe outbreaks in human populations. ZIKV infection leads to the accumulation of small non-coding viral RNAs (known as sfRNAs) that are crucial for evasion of antiviral responses and for viral pathogenesis. However, the mechanistic understanding of how sfRNAs function remains incomplete. Here, we use recombinant ZIKVs and ribosome profiling of infected human cells to show that sfRNAs block translation of antiviral genes. Mechanistically, we demonstrate that specific RNA structures present in sfRNAs trigger PKR activation, which instead of limiting viral replication, enhances viral particle production. Although ZIKV infection induces mRNA expression of antiviral genes, translation efficiency of type I interferon and interferon stimulated genes were significantly downregulated by PKR activation. Our results reveal a novel viral adaptation mechanism mediated by sfRNAs, where ZIKV increases its fitness by repurposing the antiviral role of PKR into a proviral factor.