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1.
RSC Med Chem ; 12(9): 1525-1539, 2021 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-34671736

RESUMO

The identification of specific biomarkers for Zika infection and its clinical complications is fundamental to mitigate the infection spread, which has been associated with a broad range of neurological sequelae. We present the characterization of antibody responses in serum samples from individuals infected with Zika, presenting non-severe (classical) and severe (neurological disease) phenotypes, with high-density peptide arrays comprising the Zika NS1 and NS2B proteins. The data pinpoints one strongly IgG-targeted NS2B epitope in non-severe infections, which is absent in Zika patients, where infection progressed to the severe phenotype. This differential IgG profile between the studied groups was confirmed by multivariate data analysis. Molecular dynamics simulations and circular dichroism have shown that the peptide in solution presents itself in a sub-optimal conformation for antibody recognition, which led us to computationally engineer an artificial protein able to stabilize the NS2B epitope structure. The engineered protein was used to interrogate paired samples from mothers and their babies presenting Zika-associated microcephaly and confirmed the absence of NS2B IgG response in those samples. These findings suggest that the assessment of antibody responses to the herein identified NS2B epitope is a strong candidate biomarker for the diagnosis and prognosis of Zika-associated neurological disease.

2.
Anal Bioanal Chem ; 413(19): 4873-4885, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34152457

RESUMO

The incidence of infection by the dengue virus (DENV) has grown dramatically, reaching 128 countries in tropical and subtropical regions worldwide, with a pattern of hyper-endemicity. DENV is a mosquito-borne disease having four serotypes, one or two circulating in epidemic outbreaks. The diagnosis of DENV is challenging mainly due to the circulation of new viruses with remarkable similarities, such as Zika (ZIKV) that may cause fetal microcephaly. DENV affects 390 million people per year, but these numbers may be higher due to the underreported and misclassified cases. Recently, the NS1 nonstructural protein has been described in serum and urine of DENV and ZIKV patients, suggesting its use as a biomarker for screening since a negative NS1 sample confirms the absence of these infections. Herein, a label-free immunosensor comprising an assembled nanostructured thin film of carbon nanotube-ethylenediamine is described. The advantage of in situ electrosynthesis of polymer film is to allow major control of thickness and conductivity, in addition to designing the reactive groups for functionalization. A quartz crystal microbalance system was used to estimate the thickness of the polymeric film obtained. The anti-NS1 monoclonal antibodies were immobilized to carbon nanotubes by covalent linkage, permitting a high stability during measurements. Analytical responses to NS1 were obtained by differential pulse voltammetry (DPV), showing a linear range from 20 to 800 ng mL-1 and reproducibility of 3.0%, with a limit of detection (LOD) of 6.8 ng mL- 1. This immunosensor was capable of detecting ZIKV and DENV NS1 in spiked urine and real serum in a clinical range.Graphical abstract.


Assuntos
Dengue/diagnóstico , Proteínas não Estruturais Virais/sangue , Proteínas não Estruturais Virais/urina , Infecção por Zika virus/diagnóstico , Anticorpos Imobilizados , Anticorpos Antivirais , Dengue/sangue , Dengue/urina , Técnicas Eletroquímicas , Glicoproteínas/sangue , Glicoproteínas/urina , Humanos , Imunoensaio , Membranas Artificiais , Nanoestruturas , Sensibilidade e Especificidade , Testes Sorológicos , Zika virus/imunologia , Infecção por Zika virus/sangue , Infecção por Zika virus/urina
3.
Biosensors (Basel) ; 11(5)2021 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-34065688

RESUMO

Zika virus (ZIKV) is a mosquito-borne infection, predominant in tropical and subtropical regions causing international concern due to the ZIKV disease having been associated with congenital disabilities, especially microcephaly and other congenital abnormalities in the fetus and newborns. Development of strategies that minimize the devastating impact by monitoring and preventing ZIKV transmission through sexual intercourse, especially in pregnant women, since no vaccine is yet available for the prevention or treatment, is critically important. ZIKV infection is generally asymptomatic and cross-reactivity with dengue virus (DENV) is a global concern. An innovative screen-printed electrode (SPE) was developed for amperometric detection of the non-structural protein (NS2B) of ZIKV by exploring the intrinsic redox catalytic activity of Prussian blue (PB), incorporated into a carbon nanotube-polypyrrole composite. Thus, this immunosensor has the advantage of electrochemical detection without adding any redox-probe solution (probe-less detection), allowing a point-of-care diagnosis. It was responsive to serum samples of only ZIKV positive patients and non-responsive to negative ZIKV patients, even if the sample was DENV positive, indicating a possible differential diagnosis between them by NS2B. All samples used here were confirmed by CDC protocols, and immunosensor responses were also checked in the supernatant of C6/36 and in Vero cell cultures infected with ZIKV.


Assuntos
Técnicas Biossensoriais , Imunoensaio , Zika virus/isolamento & purificação , Ferrocianetos , Humanos , Nanotubos de Carbono , Polímeros , Pirróis , Zika virus/imunologia , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/virologia
4.
Viruses ; 13(5)2021 04 23.
Artigo em Inglês | MEDLINE | ID: mdl-33922819

RESUMO

The diagnostic of arbovirus-related obstetric complications in high-risk pregnancy and childbirth care is challenging, especially in endemic areas. We conducted a prospective study to track active or recent Zika (ZIKV), dengue (DENV), or chikungunya (CHIKV) virus infection among hospitalized pregnant women (PW) with obstetric complications in a hospital at the epicenter of Zika outbreak and ZIKV-related microcephaly in Brazil. Clinical data and blood samples were collected at enrollment and 10 days after the admission of study participants, between October 2018 and May 2019. Further clinical data were extracted from medical records. Samples were screened by molecular and serological tests. Out of 780 participants, 93.1% (95% CI: 91.1-94.7%) presented previous DENV exposure (IgG). ZIKV, CHIKV, and/or DENV laboratory markers of recent or active infection were detected in 130 PW, yielding a prevalence of 16.6% (95% CI: 14.2-19.5%); 9.4% (95% CI: 7.4-11.7%), 7.4% (95% CI: 5.7-9.7%), and 0.38% (95% CI: 0.1-1.2%) of CHIKV, ZIKV, and DENV infections, respectively. Most ZIKV infections were detected by molecular assays (89.6%), while CHIKV infections were detected by serology (95.9%). Our findings highlight the need for arbovirus infections screening in PW with obstetrical complications, potentially associated to these infections in endemic areas regardless of the signs or symptoms suggestive of arboviral disease.


Assuntos
Febre de Chikungunya/epidemiologia , Vírus Chikungunya , Infecção Hospitalar/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Infecção por Zika virus/epidemiologia , Zika virus , Adolescente , Adulto , Brasil/epidemiologia , Infecção Hospitalar/virologia , Suscetibilidade a Doenças , Feminino , Humanos , Incidência , Pessoa de Meia-Idade , Gravidez , Complicações Infecciosas na Gravidez/virologia , Estudos Prospectivos , Vigilância em Saúde Pública , Fatores de Risco , Adulto Jovem
5.
Pharmaceuticals (Basel) ; 14(1)2021 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-33445640

RESUMO

Since exacerbated inflammation and microvascular leakage are hallmarks of dengue virus (DENV) infection, here we interrogated whether systemic activation of the contact/kallikrein-kinin system (KKS) might hamper endothelial function. In vitro assays showed that dextran sulfate, a potent contact activator, failed to generate appreciable levels of activated plasma kallikrein (PKa) in the large majority of samples from a dengue cohort (n = 70), irrespective of severity of clinical symptoms. Impaired formation of PKa in dengue-plasmas correlated with the presence of cleaved Factor XII and high molecular weight kininogen (HK), suggesting that the prothrombogenic contact system is frequently triggered during the course of infection. Using two pathogenic arboviruses, DENV or Zika virus (ZIKV), we then asked whether exogenous BK could influence the outcome of infection of human brain microvascular endothelial cells (HBMECs). Unlike the unresponsive phenotype of Zika-infected HBMECs, we found that BK, acting via B2R, vigorously stimulated DENV-2 replication by reverting nitric oxide-driven apoptosis of endothelial cells. Using the mouse model of cerebral dengue infection, we next demonstrated that B2R targeting by icatibant decreased viral load in brain tissues. In summary, our study suggests that contact/KKS activation followed by BK-induced enhancement of DENV replication in the endothelium may underlie microvascular pathology in dengue.

6.
Viruses ; 13(1)2021 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-33466404

RESUMO

Upper respiratory obstruction is a common sequela in children with Zika-related microcephaly (ZRM). As a cross-sectional analysis nested in a cohort study, this study aims to investigate the prevalence of adenoid hypertrophy (AH) in children with ZRM and symptoms of respiratory obstruction. The data were collected in the first three years of life from children with ZRM who were followed in two reference centers for otorhinolaryngological care of patients with congenital Zika syndrome. Out of 92 children with confirmed ZRM, 57 were evaluated by nasopharyngoscopy after presenting with upper respiratory obstruction symptoms. In this study, 31 of the 57 (54%) children with ZRM who were evaluated had obstructive AH. Thirteen children with obstructive AH were submitted to surgery, which resulted in the complete resolution of symptoms for 11, partial resolution in 1, and no improvement in 1. No evidence of direct involvement by Zika virus (ZIKV) infection in the adenoid tissues was demonstrated by histology or immunohistochemistry. Our results suggest that there is a high prevalence and early presentation of AH in children with ZRM, with consequent upper airway obstruction causing upper airway obstructive disorder, secretory otitis media, and dysphagia.


Assuntos
Tonsila Faríngea/patologia , Microcefalia/epidemiologia , Infecção por Zika virus/epidemiologia , Brasil , Pré-Escolar , Estudos de Coortes , Estudos Transversais , Feminino , Humanos , Hipertrofia/complicações , Hipertrofia/epidemiologia , Lactente , Masculino , Microcefalia/patologia , Microcefalia/virologia , Prevalência , Infecção por Zika virus/patologia
7.
J Infect Dis ; 223(4): 673-685, 2021 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32888023

RESUMO

BACKGROUND: Zika virus (ZIKV) is a mosquito-borne virus that is also transmitted sexually; however, the epidemiological relevance of ZIKV sexual transmission in endemic regions is unclear. METHODS: We performed a household-based serosurvey in Northeast Brazil to evaluate the differential exposure to ZIKV and chikungunya virus (CHIKV) among households. Individuals who participated in our previous arboviral disease cohort (indexes) were recontacted and enrolled, and their household members were newly enrolled. RESULTS: The relative risk of sexual partners being ZIKV-seropositive when living with a ZIKV-seropositive index participant was significantly higher, whereas this was not observed among nonsexual partners of the index. For CHIKV, both sexual and nonsexual partner household members living with a CHIKV-seropositive index had a significantly higher risk of being seropositive. In the nonindex-based dyadic and generalized linear mixed model analyses, the odds of sexual dyads having a concordant ZIKV plaque reduction neutralization test result was significantly higher. We have also analyzed retrospective clinical data according to the participants' exposure to ZIKV and CHIKV. CONCLUSIONS: Our data suggest that ZIKV sexual transmission may be a key factor for the high ZIKV seroprevalence among households in endemic areas and raises important questions about differential disease from the 2 modes of transmission.

9.
Talanta ; 208: 120338, 2020 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-31816752

RESUMO

Arboviruses have been emerging as a significant global health problem due to the recurrent epidemics. Arboviruses require the development of new diagnostic devices due to the nonspecific clinical manifestations. Herein, we report a biosensor based on cysteine (Cys), zinc oxide nanoparticles (ZnONp), and Concanavalin A (ConA) lectin to differentiate between arboviruses infections. ConA is capable of interacting with the saccharide components of the viral capsid. In this study, we evaluated the reproducibility, sensitivity, and specificity of the sensor for the virus of Dengue type 2 (DENV2), Zika (ZIKV), Chikungunya (CHIKV), and Yellow fever (YFV). Atomic force microscopy measurements confirmed the electrode surface modification and revealed a heterogeneous topography during the biorecognition process. Cyclic voltammetry (CV) and impedance spectroscopy (EIS) were used to characterize the biosensor. The blockage of the oxidation-reduction process is related to the formation of Cys-ZnONp-ConA system on the electroactive area and its subsequent interaction with viral glycoproteins. The sensor exhibited a linear response to different concentrations of the studied arboviruses. Our study demonstrates that ConA lectin recognizes the structural glycoproteins of the DENV2, ZIKV, CHIKV, and YFV. DENV2 is the most structurally similar to ZIKV. Our results have shown that the impedimetric response correlates with the structural glycoproteins, as follow: DENV2 (18.6 kΩ) > ZIKV (14.6 kΩ) > CHIKV (6.86 kΩ) > YFV (5.98 kΩ). The homologous structural regions contribute to ConA-arboviruses recognition. Our results demonstrate the use of the proposed system for the development of biosensors for arboviruses infections.


Assuntos
Infecções por Arbovirus/diagnóstico , Arbovírus/metabolismo , Técnicas Biossensoriais/métodos , Concanavalina A/química , Eletroquímica/métodos , Eletrodos , Nanopartículas Metálicas/química , Infecções por Arbovirus/sangue , Infecções por Arbovirus/virologia , Arbovírus/isolamento & purificação , Febre de Chikungunya/sangue , Febre de Chikungunya/diagnóstico , Febre de Chikungunya/virologia , Vírus Chikungunya/isolamento & purificação , Vírus Chikungunya/metabolismo , Cisteína/química , Dengue/sangue , Dengue/diagnóstico , Dengue/virologia , Vírus da Dengue/isolamento & purificação , Vírus da Dengue/metabolismo , Diagnóstico Diferencial , Glucose/análise , Humanos , Manose/análise , Febre Amarela/sangue , Febre Amarela/diagnóstico , Febre Amarela/virologia , Vírus da Febre Amarela/isolamento & purificação , Vírus da Febre Amarela/metabolismo , Zika virus/isolamento & purificação , Zika virus/metabolismo , Infecção por Zika virus/sangue , Infecção por Zika virus/diagnóstico , Infecção por Zika virus/virologia , Óxido de Zinco/química
10.
PLoS Negl Trop Dis ; 13(3): e0007246, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30856223

RESUMO

Laboratory confirmation of Zika virus (ZIKV) infection during pregnancy is challenging due to cross-reactivity with dengue virus (DENV) and limited knowledge about the kinetics of anti-Zika antibody responses during pregnancy. We described ZIKV and DENV serological markers and the maternal-fetal transfer of antibodies among mothers and neonates after the ZIKV microcephaly outbreak in Northeast Brazil (2016). We included 89 microcephaly cases and 173 neonate controls at time of birth and their mothers. Microcephaly cases were defined as newborns with a particular head circumference (2 SD below the mean). Two controls without microcephaly were matched by the expected date of delivery and area of residence. We tested maternal serum for recent (ZIKV genome, IgM and IgG3 anti-NS1) and previous (ZIKV and DENV neutralizing antibodies [NAbs]) markers of infection. Multiple markers of recent or previous ZIKV and DENV infection in mothers were analyzed using principal component analysis (PCA). At delivery, 5.6% of microcephaly case mothers and 1.7% of control mothers were positive for ZIKV IgM. Positivity for ZIKV IgG3 anti-NS1 was 8.0% for case mothers and 3.5% for control mothers. ZIKV NAbs was slightly higher among mothers of cases (69.6%) than that of mothers of controls (57.2%; p = 0.054). DENV exposure was detected in 85.8% of all mothers. PCA discriminated two distinct components related to recent or previous ZIKV infection and DENV exposure. ZIKV NAbs were higher in newborns than in their corresponding mothers (p<0.001). We detected a high frequency of ZIKV exposure among mothers after the first wave of the ZIKV outbreak in Northeast Brazil. However, we found low sensitivity of the serological markers to recent infection (IgM and IgG3 anti-NS1) in perinatal samples of mothers of microcephaly cases. Since the neutralization test cannot precisely determine the time of infection, testing for ZIKV immune status should be performed as early as possible and throughout pregnancy to monitor acute Zika infection in endemic areas.


Assuntos
Anticorpos Neutralizantes/sangue , Anticorpos Antivirais/sangue , Dengue/diagnóstico , Microcefalia/epidemiologia , Microcefalia/etiologia , Complicações Infecciosas na Gravidez/diagnóstico , Infecção por Zika virus/diagnóstico , Adolescente , Adulto , Brasil/epidemiologia , Estudos de Casos e Controles , Dengue/epidemiologia , Vírus da Dengue/imunologia , Feminino , Humanos , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Recém-Nascido , Masculino , Gravidez , Complicações Infecciosas na Gravidez/epidemiologia , Adulto Jovem , Zika virus/imunologia , Infecção por Zika virus/complicações , Infecção por Zika virus/epidemiologia
12.
J Virol Methods ; 257: 62-68, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29684416

RESUMO

Dengue virus (DENV) infections elicit antibody responses to the non-structural protein 1 (NS1) that are associated with protection against disease. However, the antibody isotypes and subclasses involved, and their kinetics have not been extensively studied. We characterized the antibody responses to DENV NS1 by enzyme-linked immunosorbent assay (ELISA) in a longitudinal cohort of 266 confirmed dengue cases in Recife, Northeast Brazil. Samples were collected during the febrile phase and up to over 3 years after onset of symptoms. The antibodies investigated [IgA, IgM, total IgG (all subclasses measured together) and each subclass (IgG2, IgG3 and IgG4) measured separately] had distinct kinetic profiles following primary or secondary DENV infections. Of interest, most of these antibodies were consistently detected greater than 6 months after onset of symptoms, except for IgG3. Anti-dengue NS1-specific IgG was consistently detected from the acute phase to beyond 3 years after symptom onset. In contrast, anti-dengue NS1-specific IgG3 was detected within the first week, peaked at week 2-3, and disappeared within 4-6 months after onset of symptoms. The mean duration of the IgG3 positive signal was 149 days (ranging from 126 to 172 days). In conclusion, anti-dengue NS1-specific IgG and IgG3 are potential biomarkers of long-term and recent (less than 6 months) DENV infections, respectively.


Assuntos
Anticorpos Antivirais/sangue , Biomarcadores/sangue , Vírus da Dengue/imunologia , Dengue/diagnóstico , Dengue/imunologia , Proteínas não Estruturais Virais/imunologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Criança , Pré-Escolar , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunoglobulina A/sangue , Imunoglobulina G/sangue , Imunoglobulina M/sangue , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Tempo , Adulto Jovem
13.
PLoS Negl Trop Dis ; 11(11): e0006055, 2017 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29108009

RESUMO

BACKGROUND: Several arboviruses, including dengue virus (DENV), Zika virus (ZIKV) and chikungunya virus (CHIKV), transmitted by Aedes mosquitoes, circulate in northeast Brazil. Diseases caused by these viruses are of great public health relevance, however, their epidemiological features in areas where the three viruses co-circulate are scarce. Here, we present analyses of molecular and serological diagnostics in a prospective study of acute febrile patients recruited from May 2015 to May 2016 in Recife, Brazil. METHODS: Two hundred sixty-three acute febrile patients with symptoms suggestive of an arboviral disease who attended an urgent heath care clinic in the Recife Metropolitan Region in northeast Brazil were enrolled. Acute and convalescent blood samples were collected and tested using molecular and serological assays for infection with DENV, ZIKV and CHIKV. RESULTS: Quantitative real-time reverse-transcriptase polymerase chain reactions (qRTPCR) performed on acute phase sera detected no patients positive for DENV, but 26 (9.9%) positive for ZIKV and 132 (50.2%) positive for CHIKV. There were a few suspected and only one confirmed dengue case. Specific serological assays for ZIKV and CHIKV confirmed the qRTPCR data. Analyses of DENV IgM and IgG ELISAs in the context of qRTPCR results suggested high levels of cross reactive antibodies in ZIKV-positive samples. Results from neutralization assays highly corroborated those from qRTPCR and ZIKV ELISA, indicating very few positive DENV cases. ZIKV infections were temporally clustered in the first months of the study and started to decrease concomitantly with an increase in CHIKV infections in August 2015. The proportion of CHIKV infections increased significantly in September 2015 and remained high until the end of the study period, with an average of 84.7% of recruited patients being diagnosed from August 2015 to May 2016. ZIKV infections exhibited a female bias and the cases were spread over the study site, while CHIKV cases had a male bias and were spatially clustered in each month. CONCLUSIONS: In 2015-2016 in the Recife Metropolitan Region, we detected the tail end of a Zika epidemic, which was displaced by a chikungunya epidemic. Few dengue cases were identified despite a high number of official dengue notifications in the area during this period. We show here important epidemiological features of these cases.


Assuntos
Febre de Chikungunya/epidemiologia , Surtos de Doenças , Infecção por Zika virus/epidemiologia , Adolescente , Adulto , Aedes/virologia , Idoso , Animais , Anticorpos Antivirais/sangue , Brasil/epidemiologia , Febre de Chikungunya/diagnóstico , Vírus Chikungunya/genética , Vírus Chikungunya/isolamento & purificação , Criança , Dengue/epidemiologia , Vírus da Dengue/imunologia , Vírus da Dengue/isolamento & purificação , Feminino , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Saúde Pública , Análise Espaço-Temporal , Adulto Jovem , Zika virus/genética , Zika virus/imunologia , Zika virus/isolamento & purificação , Infecção por Zika virus/diagnóstico
15.
Emerg Microbes Infect ; 6(8): e69, 2017 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-28790458

RESUMO

Zika virus (ZIKV) is a flavivirus that has recently been associated with an increased incidence of neonatal microcephaly and other neurological disorders. The virus is primarily transmitted by mosquito bite, although other routes of infection have been implicated in some cases. The Aedes aegypti mosquito is considered to be the main vector to humans worldwide; however, there is evidence that other mosquito species, including Culex quinquefasciatus, transmit the virus. To test the potential of Cx. quinquefasciatus to transmit ZIKV, we experimentally compared the vector competence of laboratory-reared Ae. aegypti and Cx. quinquefasciatus. Interestingly, we were able to detect the presence of ZIKV in the midgut, salivary glands and saliva of artificially fed Cx. quinquefasciatus. In addition, we collected ZIKV-infected Cx. quinquefasciatus from urban areas with high microcephaly incidence in Recife, Brazil. Corroborating our experimental data from artificially fed mosquitoes, ZIKV was isolated from field-caught Cx. quinquefasciatus, and its genome was partially sequenced. Collectively, these findings indicate that there may be a wider range of ZIKV vectors than anticipated.


Assuntos
Culex/virologia , Mosquitos Vetores/virologia , Replicação Viral , Zika virus/fisiologia , Aedes/virologia , Animais , Brasil/epidemiologia , Genoma Viral , Humanos , Microcefalia/epidemiologia , Mosquitos Vetores/fisiologia , Saliva/virologia , Glândulas Salivares/virologia , Análise de Sequência de DNA , Zika virus/genética , Zika virus/isolamento & purificação , Infecção por Zika virus/epidemiologia , Infecção por Zika virus/transmissão , Infecção por Zika virus/virologia
17.
Am J Med Genet A ; 173(4): 841-857, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28328129

RESUMO

In October 2015, Zika virus (ZIKV) outbreak the Brazilian Ministry of Health (MoH). In response, the Brazilian Society of Medical Genetics established a task force (SBGM-ZETF) to study the phenotype of infants born with microcephaly due to ZIKV congenital infection and delineate the phenotypic spectrum of this newly recognized teratogen. This study was based on the clinical evaluation and neuroimaging of 83 infants born during the period from July, 2015 to March, 2016 and registered by the SBGM-ZETF. All 83 infants had significant findings on neuroimaging consistent with ZIKV congenital infection and 12 had confirmed ZIKV IgM in CSF. A recognizable phenotype of microcephaly, anomalies of the shape of skull and redundancy of the scalp consistent with the Fetal Brain Disruption Sequence (FBDS) was present in 70% of infants, but was most often subtle. In addition, features consistent with fetal immobility, ranging from dimples (30.1%), distal hand/finger contractures (20.5%), and feet malpositions (15.7%), to generalized arthrogryposis (9.6%), were present in these infants. Some cases had milder microcephaly or even a normal head circumference (HC), and other less distinctive findings. The detailed observation of the dysmorphic and neurologic features in these infants provides insight into the mechanisms and timings of the brain disruption and the sequence of developmental anomalies that may occur after prenatal infection by the ZIKV.


Assuntos
Surtos de Doenças , Doenças Fetais/epidemiologia , Microcefalia/epidemiologia , Complicações Infecciosas na Gravidez/epidemiologia , Infecção por Zika virus/epidemiologia , Anticorpos Antivirais/líquido cefalorraquidiano , Encéfalo/anormalidades , Encéfalo/virologia , Brasil/epidemiologia , Feminino , Doenças Fetais/diagnóstico por imagem , Doenças Fetais/patologia , Feto , Humanos , Imunoglobulina G/líquido cefalorraquidiano , Lactente , Microcefalia/complicações , Microcefalia/diagnóstico por imagem , Microcefalia/patologia , Neuroimagem , Gravidez , Complicações Infecciosas na Gravidez/diagnóstico , Complicações Infecciosas na Gravidez/patologia , Síndrome , Zika virus/crescimento & desenvolvimento , Zika virus/imunologia , Zika virus/patogenicidade , Infecção por Zika virus/complicações , Infecção por Zika virus/diagnóstico por imagem , Infecção por Zika virus/patologia
18.
J Infect Dis ; 215(5): 781-785, 2017 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-28039355

RESUMO

Anti-Flavivirus antibodies are highly cross-reactive and may facilitate Zika virus (ZIKV) infection through the antibody-dependent enhancement (ADE) mechanism. We demonstrate that dengue-specific antibodies enhance the infection of a primary Brazilian ZIKV isolate in a FcγRII-expressing K562 cell line. In addition, we demonstrate that serum samples from dengue-immune pregnant women enhanced ZIKV infection. These findings highlight the need for epidemiological studies and animal models to further confirm the role of ADE in the development of congenital and neurological complications associated with ZIKV infections.


Assuntos
Anticorpos Antivirais/sangue , Anticorpos Facilitadores , Vírus da Dengue , Infecção por Zika virus/imunologia , Zika virus/patogenicidade , Anticorpos Antivirais/imunologia , Antivirais/farmacologia , Brasil , Reações Cruzadas , Feminino , Humanos , Células K562 , Gravidez , Receptores de IgG/imunologia , Infecção por Zika virus/sangue
19.
ACS Omega ; 2(7): 3913-3920, 2017 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-30023708

RESUMO

B-cell epitope sequences from Zika virus (ZIKV) NS1 protein have been identified using epitope prediction tools. Mapping these sequences onto the NS1 surface reveals two major conformational epitopes and a single linear one. Despite an overall average sequence identity of ca. 55% between the NS1 from ZIKV and the four dengue virus (DENV) serotypes, epitope sequences were found to be highly conserved. Nevertheless, nonconserved epitope-flanking residues are responsible for a dramatically divergent electrostatic surface potential on the epitope regions of ZIKV and DENV2 serotypes. These findings suggest that strategies for differential diagnostics on the basis of short linear NS1 sequences are likely to fail due to immunological cross-reactions. Overall, results provide the molecular basis of differential discrimination between Zika and DENVs by NS1 monoclonal antibodies.

20.
F1000Res ; 5: 2523, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27909576

RESUMO

Background The recent epidemics of Zika virus (ZIKV) implicated it as the cause of serious and potentially lethal congenital conditions such microcephaly and other central nervous system defects, as well as the development of the Guillain-Barré syndrome in otherwise healthy patients. Recent findings showed that anti-Dengue antibodies are capable of amplifying ZIKV infection by a mechanism similar to antibody-dependent enhancement, increasing the severity of the disease. This scenario becomes potentially catastrophic when the global burden of Dengue and the advent of the newly approved anti-Dengue vaccines in the near future are taken into account. Thus, antiviral chemotherapy should be pursued as a priority strategy to control the spread of the virus and prevent the complications associated with Zika. Methods Here we describe a fast and reliable cell-based, high-content screening assay for discovery of anti-ZIKV compounds. This methodology has been used to screen the National Institute of Health Clinical Collection compound library, a small collection of FDA-approved drugs. Results and conclusion From 725 FDA-approved compounds triaged, 29 (4%) were found to have anti-Zika virus activity, of which 22 had confirmed (76% of confirmation) by dose-response curves. Five candidates presented selective activity against ZIKV infection and replication in a human cell line. These hits have abroad spectrum of chemotypes and therapeutic uses, offering valuable opportunities for selection of leads for antiviral drug discovery.

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