Navegando por Palavras-chave "Zika virus"
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- ItemAcesso aberto (Open Access)Avaliação das etapas de ativação dos inflamassomas em astrócitos em resposta ao Zika vírus(Universidade Federal de São Paulo, 2023-12-12) Lucena, Victoria Weise Leite de [UNIFESP]; Bortoluci, Karina Ramalho [UNIFESP]; lattes.cnpq.br/0159648961678651; http://lattes.cnpq.br/5323032126001718Os inflamassomas são complexos citosólicos multiproteicos ativados em resposta a infecções ou danos celulares. A ativação dessas plataformas leva ao recrutamento e autoclivagem da protease efetora caspase-1 e consequente liberação de IL-1β e IL-18, além da indução de uma forma específica de morte celular, a piroptose. Esses complexos são encontrados em diversas células imunes como os macrófagos, neutrófilos e células dendríticas, mas sua presença já foi caracterizada em outras células, como em células epiteliais e no Sistema Nervoso Central (SNC). No SNC, os inflamassomas participam do controle de infecções, mas também estão relacionados a patologias como Doenças neurodegenerativas e Transtornos neuropsiquiátricos. A maior parte dos estudos de inflamassomas no SNC é limitada às micróglias, visto que estas células compõem o principal eixo imune desse compartimento. Os astrócitos se encontram em grande quantidade no SNC, possuindo funções essenciais para o funcionamento dos circuitos neurais e metabolismo do SNC. Por mais que a expressão de inflamassomas e de seus componentes já tenha sido documentada em astrócitos, não se sabe com clareza as etapas e mecanismos que levam a sua ativação, especialmente no contexto infeccioso. Por isso, o presente trabalho buscou avaliar a participação dos inflamassomas de astrócitos primários murinos durante a infecção por Zika vírus (ZIKV), através da análise de expressão, montagem e funcionalidade dos inflamassomas. Para isso, as células foram divididas em grupos tratados ou não tratados com LPS e infectadas com ZIKV em multiplicidade de infecção (MOI) 1 por 2 horas, 24 horas, 48 horas ou 72 horas. Através de imagens de imunofluorescência, não foi observada a formação de punctas de ASC em nenhum dos tempos de infecção analisados. Astrócitos infectados por ZIKV não apresentaram secreção de IL-1β. Através da dosagem de lactato, foi observado um aumento de sua concentração no decorrer do tempo, mas não foram encontradas diferenças no metabolismo glicolítico entre astrócitos infectados e não infectados. Não houve diferenças significativas entre os grupos tratados e não tratados com LPS em nenhum dos testes realizados. Os dados obtidos sugerem que o ZIKV não é capaz de induzir a ativação dos inflamassomas em astrócitos, indicando um mecanismo não dependente da resposta clássica dos inflamassomas no controle dessa infecção.
- ItemAcesso aberto (Open Access)Caracterização das manifestações oftalmológicas na síndrome congênita do zika vírus(Universidade Federal de São Paulo (UNIFESP), 2018-01-18) Ventura, Camila Vieira Oliveira Carvalho [UNIFESP]; Maia, Mauricio [UNIFESP]; Mattos Júnior, Rubens Belfort [UNIFESP]; http://lattes.cnpq.br/4270399167335564; http://lattes.cnpq.br/6377105744231862; http://lattes.cnpq.br/4175503620317639; Universidade Federal de São Paulo (UNIFESP)Objectives: To characterize the ocular abnormalities identified in infants with Congenital Zika Syndrome (CZS). For this purpose, three studies were conducted with the following specific objectives: 1 - To describe the ocular findings identified in infants with microcephaly exposed to the Zika virus (ZIKV) during pregnancy; 2 - To determine the risk factors related to ocular manifestations of SCZV; 3 - To analyze the retinal layers affected by the ZIKV using Optical Coherence Tomography (OCT). Methods: Infants with microcephaly and/or other neurological findings suggestive of congenital infection born between May and December 2015 in the state of Pernambuco were included in this line of research. Children who were positive serologically for any other congenital infection including toxoplasmosis, rubella, cytomegalovirus, herpes, syphilis, and HIV were excluded. In the three studies, all infants and their respective mothers underwent a thorough ophthalmic evaluation and fundus documentation using RetCam Shuttle® (Natus Medical Inc., USA). Results: The first study described the ocular morphological findings of 10 newborns with funduscopic findings and presumed diagnosis of CZSV. Anterior segment examination was normal in all patients. As for the ocular motility, 1 child (10.0%) presented horizontal nystagmus, 4 (40.0%) exophoria and 2 (20.0%) esophoria. In addition, 17 eyes (85.0%) presented with optic nerve and/or retina findings. The optic nerve findings were detected in 9 eyes (45.0%) and included disc hypoplasia, pallor, and increased disc cupping. Retinal abnormalities were detected in 16 eyes (80.0%) and included loss of foveal reflex, mild to gross focal pigmentation mottling, and well-defined chorioretinal scars. In the second study, 24 infants (60.0%) had their diagnosis confirmed using the serological test. Funduscopic findings were observed in 37 (46.3%) eyes of 22 (55.0%) infants. For statistical purposes, the children were divided into two groups: those with and those without ocular manifestations. The risk factors identified in this study were severe microcephaly at birth (frequency, -1.50; 95% CI, -2.56 to -0.51; P = 0.004) and the trimester when the maternal infection occurred (frequency, 0,36; 95% CI, 0.02-0.67; P = 0.04). The third study evaluated the affected retinal layers in eight eyes with chorioretinal scars using the OCT. The main findings of OCT included discontinuation of the ellipsoid zone and hyper-reflectivity underlying the retinal pigment epithelium in 9 eyes (100%), retinal thinning in 8 eyes (89.0%), choroidal thinning in 7 eyes (78.0%) and a colobomatous-like appearance in 4 eyes (44.0%). Conclusions: 1 - The main ocular lesions identified in children with CZS were focal pigment mottling and chorioretinal atrophy with a predilection for the macula, and optic disc abnormalities, including optic disc pallor, hypoplasia, and increased disc cupping. 2 - Ocular involvement in infants with presumed CZS was more frequently seen in infants with smaller cephalic diameter at birth and in infants whose mothers reported symptoms during the first trimester. 3 - Zika virus may cause severe damage to the retina, including the internal and external layers, as well as the choroid.
- ItemAcesso aberto (Open Access)Epitope Sequences in Dengue Virus NS1 Protein Identified by Monoclonal Antibodies(Mdpi Ag, 2017) Rocha, Leticia Barboza; dos Santos Alves, Rubens Prince; Caetano, Bruna Alves; Pereira, Lennon Ramos; Mitsunari, Thais; Amorim, Jaime Henrique; Polatto, Juliana Moutinho; Botosso, Viviane Fongaro; Frazatti Gallina, Neuza Maria; Palacios, Ricardo; Precioso, Alexander Roberto; Hernandes Granato, Celso Francisco [UNIFESP]; Leal Oliveira, Danielle Bruna; da Silveira, Vanessa Barbosa; Luz, Daniela; de Souza Ferreira, Luis Carlos; Fontes Piazza, Roxane MariaDengue nonstructural protein 1 (NS1) is a multi-functional glycoprotein with essential functions both in viral replication and modulation of host innate immune responses. NS1 has been established as a good surrogate marker for infection. In the present study, we generated four anti-NS1 monoclonal antibodies against recombinant NS1 protein from dengue virus serotype 2 (DENV2), which were used to map three NS1 epitopes. The sequence (193)AVHADMGYWIESALNDT(209) was recognized by monoclonal antibodies 2H5 and 4H1BC, which also cross-reacted with Zika virus (ZIKV) protein. On the other hand, the sequence (25)VHTWTEQYKFQPES(38) was recognized by mAb 4F6 that did not cross react with ZIKV. Lastly, a previously unidentified DENV2 NS1-specific epitope, represented by the sequence (127)ELHNQTFLIDGPETAEC(143), is described in the present study after reaction with mAb 4H2, which also did not cross react with ZIKV. The selection and characterization of the epitope, specificity of anti-NS1 mAbs, may contribute to the development of diagnostic tools able to differentiate DENV and ZIKV infections.
- ItemSomente MetadadadosHigh-resolution structure of a Kazal-type serine protease inhibitor from the dengue vector Aedes aegypti(Int Union Crystallography, 2017) Torquato, Ricardo J. S. [UNIFESP]; Lu, Stephen [UNIFESP]; Martins, Nadia Helena; Tanaka, Aparecida S. [UNIFESP]; Barbosa Pereira, Pedro JoseBlood-feeding exoparasites are rich sources of protease inhibitors, and the mosquito Aedes aegypti, which is a vector of Dengue virus, Yellow fever virus, Chikungunya virus and Zika virus, is no exception. AaTI is a single-domain, noncanonical Kazal-type serine proteinase inhibitor from A. aegypti that recognizes both digestive trypsin-like serine proteinases and the central protease in blood clotting, thrombin, albeit with an affinity that is three orders of magnitude lower. Here, the 1.4 angstrom resolution crystal structure of AaTI is reported from extremely tightly packed crystals (similar to 22% solvent content), revealing the structural determinants for the observed inhibitory profile of this molecule.
- ItemSomente MetadadadosOcular effects of Zika virus-a review(Elsevier Science Inc, 2018) Marquezan, Maria Carolina [UNIFESP]; Ventura, Camila V. [UNIFESP]; Sheffield, Jeanne S.; Golden, William Christopher; Omiadze, Revaz; Belfort, Rubens, Jr. [UNIFESP]; May, WilliamZika virus was considered an innocent pathogen while restricted to the African and Asian population
- ItemSomente MetadadadosOn the origin and timing of Zika virus introduction in Brazil(Cambridge Univ Press, 2017) Massad, E.; Burattini, Marcelo Nascimento [UNIFESP]; Khan, K.; Struchiner, C. J.; Coutinho, F. A. B.; Wilder-Smith, A.The timing and origin of Zika virus (ZIKV) introduction in Brazil has been the subject of controversy. Initially, it was assumed that the virus was introduced during the FIFA World Cup in June-July 2014. Then, it was speculated that ZIKV may have been introduced by athletes from French Polynesia (FP) who competed in a canoe race in Rio de Janeiro in August 2014. We attempted to apply mathematical models to determine the most likely time window of ZIKV introduction in Brazil. Given that the timing and origin of ZIKV introduction in Brazil may be a politically sensitive issue, its determination (or the provision of a plausible hypothesis) may help to prevent undeserved blame. We used a simple mathematical model to estimate the force of infection and the corresponding individual probability of being infected with ZIKV in FP. Taking into account the air travel volume from FP to Brazil between October 2013 and March 2014, we estimated the expected number of infected travellers arriving at Brazilian airports during that period. During the period between December 2013 and February 2014, 51 individuals travelled from FP airports to 11 Brazilian cities. Basing on the calculated force of ZIKV infection (the per capita rate of new infections per time unit) and risk of infection (probability of at least one new infection), we estimated that 18 (95% CI 12-22) individuals who arrived in seven of the evaluated cities were infected. When basic ZIKV reproduction numbers greater than one were assumed in the seven evaluated cities, ZIKV could have been introduced in any one of the cities. Based on the force of infection in FP, basic reproduction ZIKV number in selected Brazilian cities, and estimated travel volume, we concluded that ZIKV was most likely introduced and established in Brazil by infected travellers arriving from FP in the period between October 2013 and March 2014, which was prior to the two aforementioned sporting events.
- ItemAcesso aberto (Open Access)Potencial diagnóstico e vacinal de derivados da proteína de envelope (E) do vírus Zika produzidos em procarioto e eucarioto(Universidade Federal de São Paulo, 2022-12-01) Lunardelli, Victória Alves Santos [UNIFESP]; Rosa, Daniela Santoro [UNIFESP]; Boscardin, Silvia Beatriz [UNIFESP]; http://lattes.cnpq.br/0930830632147222; http://lattes.cnpq.br/1472798853821902; http://lattes.cnpq.br/4241130043577573No presente estudo, avaliamos o potencial diagnóstico e vacinal de diferentes proteínas recombinantes do vírus Zika (ZIKV) produzidas em sistema procarioto (Eschericha coli) e eucarioto (células S2 de Drosophila melanogaster). A glicoproteína do envelope do ZIKV (EZIKV) é responsável pela entrada do vírus nas células hospedeiras, é o principal alvo dos anticorpos neutralizantes e por esse motivo tem sido utilizada como antígeno alvo tanto em testes sorológicos quanto para o desenvolvimento de vacinas de subunidade. A EZIKV é composta por três domínios estruturais e funcionais (EDI, EDII e EDIII), que possuem elevada homologia com as correspondentes presentes em outros flavivírus, particularmente com os diferentes sorotipos de vírus da dengue (DENV). Inicialmente realizamos uma análise da imunogenicidade das proteínas recombinantes expressas em procarioto em duas diferentes linhagens de camundongos (C57Bl/6 e BALB/c). A imunização induziu títulos elevados de anticorpos E-específicos que reconheceram células infectadas com ZIKV e neutralizaram o vírus. Além disso, a imunização com as proteínas EZIKV, EDI/IIZIKV e EDIIIZIKV induziu células produtoras de IFNg específicas e linfócitos T CD4+ e CD8+ produtores de citocinas. Em adição, identificamos 4 peptídeos presentes na proteína do envelope (E1-20, E51-70, E351-370 e E361- db 380), capazes de induzir uma resposta imune celular nos haplótipos H-2K e H-2K . Avaliamos a modulação da resposta imune humoral frente a imunização na presença de diferentes adjuvantes (poly (I:C), AddaVax, Quil-A, Alhydrogel e CpG ODN). Observamos que a imunização com a EZIKV ou EDIIIZIKV na presença do adjuvante AddaVax induziu maior título de anticorpos neutralizantes quando comparada aos demais grupos. Realizamos uma comparação sistemática da antigenicidade e imunogenicidade de EZIKV, EDI/IIZIKV e EDIIIZIKV expressas no sistema procarioto e eucarioto. A análise com amostras de soro de participantes infectados por ZIKV e DENV demonstrou que as proteínas EZIKV e EDIIIZIKV produzidas em procarioto apresentaram melhor sensibilidade e especificidade em relação às proteínas produzidas em eucarioto. Análises in vivo foram realizadas com camundongos C57Bl/6 e mostraram que, apesar de apresentarem imunogenicidade semelhante, os antígenos produzidos em células S2, particularmente EZIKV e EDIIIZIKV, induziram níveis mais elevados de anticorpos neutralizantes nos camundongos vacinados. Além disso, a imunização com EZIKV expressa em células S2 retardou o aparecimento dos sintomas e aumentou as taxas de sobrevivência em camundongos imunocomprometidos após o desafio com ZIKV. Todos os antígenos recombinantes, produzidos em bactérias ou células de insetos, induziram respostas de células T CD4+ e CD8+ específicas. Em conclusão, o presente estudo demonstrou o potencial uso diagnóstico e vacinal de antígenos recombinantes de ZIKV produzidos em dois sistemas de expressão de proteínas heterólogas. Demonstramos que antígenos produzidos no sistema procarioto apresentaram melhor desempenho em testes diagnósticos, enquanto os produzidos em sistema eucarioto apresentaram maior potencial como imunógenos.
- ItemSomente MetadadadosZika virus and pregnancy in Brazil: What happened?(Galenos Yayincilik, 2018) Pereira, Alessandra Mendelski; Maia Monteiro, Denise Leite; Werner, Heron; Daltro, Pedro; Fazecas, Tatiana; Guedes, Bianca; Tonni, Gabriele; Peixoto, Alberto Borges; Araujo Junior, Edward [UNIFESP]The recent epidemic of Zika virus (ZIKV) infection in Central and South America is one of the most serious global public health emergencies since the Ebola outbreak in West Africa. In Brazil, especially in the north, northeast, and southeast parts of the country, the ZIKV outbreak is a cause of concern for pregnant women because ZIKV intrauterine infection has been found to be associated with multiple brain malformations and microcephaly. In Brazil, the number of newborns with confirmed microcephaly per year recorded during the ZIKV outbreak, has been approximately 15 times greater than previously reported. Considering that the infection is self-limiting and symptomatic, it is usually diagnosed at the time of routine prenatal scan, especially in the third trimester. In other cases, the disease is detected after childbirth through neuroimaging. This study provides an insight into the history and evolution of ZIKV in Brazil, including current knowledge concerning the transmission, diagnosis, and pathogenesis of the infection. In addition, this review describes the pre-and postnatal neuroimaging findings obtained using ultrasound, magnetic resonance imaging, and computed tomography.
- ItemSomente MetadadadosZika virus and the eye(Lippincott Williams & Wilkins, 2017) Freitas, Bruno de Paula [UNIFESP]; Ventura, Camila V. [UNIFESP]; Maia, Mauricio [UNIFESP]; Belfort, Rubens, Jr. [UNIFESP]Purpose of review The aim of this study was to review the ocular findings related to the Zika virus (ZIKV) based on the main studies published to date, describe the patterns of the lesions and risk factors, and identify the public health implications and scientific importance of this emerging disease. Recent findings In most studies, the ZIKV seems related to congenital ocular lesions and most mothers reported mild symptoms during the first pregnancy trimester. Five fundus patterns were seen most often: macular chorioretinal atrophy, chorioretinal atrophy elsewhere, focal pigmentary changes in the macular region, optic nerve abnormalities and combined types. A few studies have suggested that the ZIKV might damage the anterior segment of these babies' eyes. Few reports have described the ocular complications seen in adults during the acute infection, including conjunctivitis, iridocyclitis and chorioretinitis. Summary Infants with congenital Zika syndrome might have vision-threatening fundus abnormalities. Although the full spectrum of ocular lesions caused by the ZIKV infection is not yet determined, a distinctive new disease has been observed. Recognition of these lesions by ophthalmologists can help ensure appropriate etiologic evaluation and clinical investigation to define the range of anomalies in an affected infant and determine essential follow-up and ongoing care.
- ItemAcesso aberto (Open Access)Zika Virus Outbreak - Should assisted reproduction patients avoid pregnancy?(Soc Brasileira Reproducao Assistida-Sbra, 2017) Borges, Edson, Jr.; de Almeida Ferreira Braga, Daniela Paes [UNIFESP]; Zanetti, Bianca Ferrarini; Setti, Amanda Souza; Provenza, Rodrigo Rosa; Iaconelli, Assumpto, Jr.Objective: To discuss the requirement from the National Health Surveillance Agency(ANVISA), for assisted reproduction treatment patients to undergo laboratory tests for ZIKV detection, and if the public health authorities and government leaders' recommendations to women simply avoid pregnancy is prudent. Methods: This study was performed in a universityaffiliated in vitro fertilization center in Brazil. We present a critical discussion on the risk of microcephaly due to ZIKV infection and the prevalence of other harmful pathogens to vulnerable pregnant women and infants. We assessed, 954 patients undergoing intracytoplasmic sperm injection cycles(ICSI), between April and November of 2016, concerning the results of ZIKV test, according to different regions in Brazil. Results: Patients undergoing ICSI cycles were split into groups, according to their region of origin: 28(3.0%) were from the North, 27(2.8%) were from the Northeast, 40(4.2%) were from the Midwest, 830(87.2%) were from the Southeast, and 29(3.0%) were from the South. Concerning the diagnosis, 112 samples had a positive or inconclusive result for ZIKV, by chromatography immunoassay. These samples were re-analyzed by ELISA and no result was positive. All positive results were from the Southeast region and none from the Northeast or Midwest regions, which are considered endemic regions. Conclusion: ZIKV test before the onset of assisted reproduction treatments does not rule out the risk of the infection during pregnancy. In addition, although ZIKV infection risk is extremely high, the microcephaly risk due to ZIKV is not higher than the risk of miscarriage and birth defects due to other recognized pathogens.