Desdobramentos dos surtos de infecção pelo vírus Zika

O vírus Zika (ZIKV) é um vírus emergente transmitido por artrópodes que apenas recentemente foi exposto como uma ameaça substancial à saúde pública. O surto de ZIKV no Brasil, especialmente, e sua associação com anormalidades fetais têm levado a preocupação mundial. Esta revisão propõe trazer ao leitor as últimas consequências no mundo e os esforços da comunidade científica para elucidar melhor a transmissão e a patogenia desta doença. Aqui, resumimos esses estudos, incluindo a epidemiologia ZIKV, aspectos virais, transmissão, características e estudos sobre o possível desenvolvimento de novas terapias e vacinas

The Innate Defense in the Zika-Infected Placenta

Zika virus (ZIKV) is an arthropod-borne virus that belongs to the Flaviviridae family, genus Flavivirus and was first isolated 1947 in Uganda, Africa, from the serum of a sentinel Rhesus monkey. Since its discovery, the virus was responsible for major outbreaks in several different countries, being linked to severe complications in pregnant women, neonatal birth defects and the congenital zika syndrome. Maternal–fetal transmission of ZIKV can occur in all trimesters of pregnancy, and the role of the placenta and its cells in these cases is yet to be fully understood. The decidua basalis and chorionic villi, maternal–fetal components of the placenta, contain a rich immunological infiltrate composed by Hofbauer cells, mastocytes, dendritic cells and macrophages, primary cells of the innate immune response that have a role that still needs to be better investigated in ZIKV infection. Recent studies have already described several histopathological features and the susceptibility and permissiveness of placenta cells to infection by the Zika virus. In this review, we address some of the current knowledge on the innate immune responses against ZIKV, especially in the placenta

The Innate Immune Response in DENV- and CHIKV-Infected Placentas and the Consequences for the Fetuses: A Minireview

Dengue virus (DENV) and chikungunya (CHIKV) are arthropod-borne viruses belonging to the Flaviviridae and Togaviridae families, respectively. Infection by both viruses can lead to a mild indistinct fever or even lead to more severe forms of the diseases, which are characterized by a generalized inflammatory state and multiorgan involvement. Infected mothers are considered a high-risk group due to their immunosuppressed state and the possibility of vertical transmission. Thereby, infection by arboviruses during pregnancy portrays a major public health concern, especially in countries where epidemics of both diseases are regular and public health policies are left aside. Placental involvement during both infections has been already described and the presence of either DENV or CHIKV has been observed in constituent cells of the placenta. In spite of that, there is little knowledge regarding the intrinsic earlier immunological mechanisms that are developed by placental cells in response to infection by both arboviruses. Here, we approach some of the current information available in the literature about the exacerbated presence of cells involved in the innate immune defense of the placenta during DENV and CHIKV infections

Dataset of proteins mapped on HepG2 cells and those differentially abundant after expression of the dengue non-structural 1 protein

Submitted by Sandra Infurna ([email protected]) on 2017-07-06T11:18:28Z No. of bitstreams: 1 kissila_rabello_etal_IOC_2017.pdf: 242955 bytes, checksum: 46636369b4ac26eee8399580fb957a75 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2017-07-06T11:32:00Z (GMT) No. of bitstreams: 1 kissila_rabello_etal_IOC_2017.pdf: 242955 bytes, checksum: 46636369b4ac26eee8399580fb957a75 (MD5)Made available in DSpace on 2017-07-06T11:32:00Z (GMT). No. of bitstreams: 1 kissila_rabello_etal_IOC_2017.pdf: 242955 bytes, checksum: 46636369b4ac26eee8399580fb957a75 (MD5) Previous issue date: 2017-02Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biotecnologia e Fisiologia das Infecções Virais. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Toxinologia. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biotecnologia e Fisiologia das Infecções Virais. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Toxinologia. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Laboratório de Proteômica e Engenharia de Proteínas. Curitiba, PR, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Toxinologia. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biotecnologia e Fisiologia das Infecções Virais. Rio de Janeiro, RJ. Brasil.The data supplied in this article are related to the research article entitled "The effect of the dengue non-structural 1 protein expression over the HepG2 cell proteins in a proteomic approach" (K. Rabelo, M.R. Trugillo, S.M. Costa, B.A. Pereira, O.C. Moreira, A.T. Ferreira et al., 2016) [1]. The present article provides the inventory of peptides and proteins mapped in a hepatocyte cell line (HepG2) by mass spectrometry in the presence of the non-structural protein 1 (NS1) of Dengue 2 virus (DENV2). Cells were transfected with pcENS1 plasmid, which encodes the DENV2 NS1 protein, or the controls pcDNA3 (negative control) or pMAXGFP, encoding the green fluorescent protein (GFP), a protein unrelated to dengue. Differentially abundant protein lists were obtained by comparing cells transfected with pcENS1 and controls

Aliskiren improves renal morphophysiology and inflammation in Wistar rats with 2K1C renovascular hypertension

Hypertension is characterized by persistent elevated blood pressure levels, one of the leading causes of death in the world. Renovascular hypertension represents the most common cause of secondary hypertension, and its progress is associated with overactivation of the renin angiotensin aldosterone system (RAAS), causing systemic and local changes. Aliskiren is a renin-inhibiting drug that optimizes RAAS suppression. In this sense, the objective of the present study was to analyze the morphophysiology of the left kidney in Wistar rats with renovascular hypertension after treatment with Aliskiren. Parameters such as systolic blood pressure, urinary creatinine and protein excretion, renal cortex structure and ultrastructure, fibrosis and tissue inflammation were analyzed. Our results showed that the hypertensive animals treated with Aliskiren presented a reestablishment of blood pressure, expression of renin, and renal function, as well as a remodeling of morphological alterations through the reduction of fibrosis. The treatment regulated the laminin expression and decreased pro-inflammatory cytokines, restoring the integrity of the glomerular filtration barrier. Therefore, our findings suggest that Aliskiren has a renoprotective effect acting on the improvement of the morphology, physiology and pathology of the renal cortex of animals with renovascular hypertensio

SARS-CoV-2 Is Persistent in Placenta and Causes Macroscopic, Histopathological, and Ultrastructural Changes

SARS-CoV-2 is a virus that belongs to the Betacoronavirus genus of the Coronaviridae family. Other coronaviruses, such as SARS-CoV and MERS-CoV, were associated with complications in pregnant women. Therefore, this study aimed to report the clinical history of five pregnant women infected with SARS-CoV-2 (four symptomatic and one asymptomatic who gave birth to a stillborn child) during the COVID-19 pandemic. They gave birth between August 2020 to January 2021, a period in which there was still no vaccination for COVID-19 in Brazil. In addition, their placental alterations were later investigated, focusing on macroscopic, histopathological, and ultrastructural aspects compared to a prepandemic sample. Three of five placentas presented SARS-CoV-2 RNA detected by RT-PCRq at least two to twenty weeks after primary pregnancy infection symptoms, and SARS-CoV-2 spike protein was detected in all placentas by immunoperoxidase assay. The macroscopic evaluation of the placentas presented congested vascular trunks, massive deposition of fibrin, areas of infarctions, and calcifications. Histopathological analysis showed fibrin deposition, inflammatory infiltrate, necrosis, and blood vessel thrombosis. Ultrastructural aspects of the infected placentas showed a similar pattern of alterations between the samples, with predominant characteristics of apoptosis and detection of virus-like particles. These findings contribute to a better understanding of the consequences of SARS-CoV-2 infection in placental tissue, vertical transmission

Evidence for Tissue Toxicity in BALB/c Exposed to a Long-Term Treatment with Oxiranes Compared to Meglumine Antimoniate

Submitted by Sandra Infurna ([email protected]) on 2017-11-30T15:03:03Z No. of bitstreams: 1 luizfilipe_oliveira_etal_IOC_2017.pdf: 13582294 bytes, checksum: 884ee7892f0c8033aa9f9268a38130c7 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2017-11-30T15:19:55Z (GMT) No. of bitstreams: 1 luizfilipe_oliveira_etal_IOC_2017.pdf: 13582294 bytes, checksum: 884ee7892f0c8033aa9f9268a38130c7 (MD5)Made available in DSpace on 2017-11-30T15:19:55Z (GMT). No. of bitstreams: 1 luizfilipe_oliveira_etal_IOC_2017.pdf: 13582294 bytes, checksum: 884ee7892f0c8033aa9f9268a38130c7 (MD5) Previous issue date: 2017Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Imunoparasitologia. Rio de Janeiro, RJ. Brasil.Universidade do Estado do Rio de Janeiro. Instituto de Biologia Roberto Alcântara Gomes. Laboratório de Ultraestrutura e Biologia Tecidual. Rio de Janeiro, RJ, Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Laboratório de Tecnologia Virológica,.Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto de Tecnologia em Imunobiológicos. Laboratório de Tecnologia Virológica,.Rio de Janeiro, RJ. Brasil.Universidade Federal Fluminense. Instituto de Biologia. Niterói, RJ, Brasil.Universidade Federal Fluminense. Instituto de Química. Departamento de Química Orgânica. Niterói, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisas Médicas. Rio de Janeiro, RJ. Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia Molecular e Doenças Endêmicas. Rio de Janeiro, RJ. Brasil.Leishmaniasis remains a serious public health problem in developing countries without effective control, whether by vaccination or chemotherapy. Part of the failure of leishmaniasis control is due to the lack of new less toxic and more effective drugs able to eliminate both the lesions and the parasite. Oxiranes derived from naphthoquinones now being assayed are promising drugs for the treatment of this group of diseases. The predicted pharmacokinetic properties and toxicological profiles of epoxy-α-lapachone and epoxymethoxy-lawsone have now been compared to those of meglumine antimoniate, and histological changes induced by these drugs in noninfected BALB/c mice tissues are described. Effects of these compounds on liver, kidney, lung, heart, and cerebral tissues of healthy mice were examined. The data presented show that both these oxiranes and meglumine antimoniate induce changes in all BALB/c mice tissues, with the lung, heart, and brain being the most affected. Epoxymethoxy-lawsone was the most toxic to lung tissue, while most severe damage was caused in the heart by epoxy-α-lapachone. Meglumine antimoniate caused mild-to-moderate changes in heart and lung tissues

Dengue virus nonstructural 3 protein interacts directly with human glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and reduces its glycolytic activity

Submitted by Sandra Infurna ([email protected]) on 2019-05-02T15:36:16Z No. of bitstreams: 1 Marciano_Paes_etal_IOC_2019.pdf: 2757474 bytes, checksum: f484f68c0e57cb9176253927e0d15291 (MD5)Approved for entry into archive by Sandra Infurna ([email protected]) on 2019-05-02T15:49:17Z (GMT) No. of bitstreams: 1 Marciano_Paes_etal_IOC_2019.pdf: 2757474 bytes, checksum: f484f68c0e57cb9176253927e0d15291 (MD5)Made available in DSpace on 2019-05-02T15:49:17Z (GMT). No. of bitstreams: 1 Marciano_Paes_etal_IOC_2019.pdf: 2757474 bytes, checksum: f484f68c0e57cb9176253927e0d15291 (MD5) Previous issue date: 2019Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Genômica Estrutural. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Genômica Estrutural. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Faculdade de Farmácia. Departamento de Biotecnologia Farmacêutica. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Genômica Estrutural. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Genômica Estrutural. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Genômica Estrutural. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biodiversidade e Sustentabilidade. Macaé, RJ, Brasil.Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório Interdisciplinar de Pesquisa Médica. Rio de Janeiro, RJ. Brasil.Universidade do Estado do Rio de Janeiro. Laboratório de Ultraestrutura e Biologia Tecidual. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Física Biológica. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Física Biológica. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Biofísica Carlos Chagas Filho. Laboratório de Genômica Estrutural. Rio de Janeiro, RJ, Brasil.Dengue is an important mosquito-borne disease and a global public health problem. The disease is caused by dengue virus (DENV), which is a member of the Flaviviridae family and contains a positive single-stranded RNA genome that encodes a single precursor polyprotein that is further cleaved into structural and non-structural proteins. Among these proteins, the non-structural 3 (NS3) protein is very important because it forms a non-covalent complex with the NS2B cofactor, thereby forming the functional viral protease. NS3 also contains a C-terminal ATPase/helicase domain that is essential for RNA replication. Here, we identified 47 NS3-interacting partners using the yeast two-hybrid system. Among those partners, we highlight several proteins involved in host energy metabolism, such as apolipoprotein H, aldolase B, cytochrome C oxidase and glyceraldehyde-3-phosphate dehydrogenase (GAPDH). GAPDH directly binds full-length NS3 and its isolated helicase and protease domains. Moreover, we observed an intense colocalization between the GAPDH and NS3 proteins in DENV2-infected Huh7.5.1 cells, in NS3-transfected BHK-21 cells and in hepatic tissue from a fatal dengue case. Taken together, these results suggest that the human GAPDH-DENV NS3 interaction is involved in hepatic metabolic alterations, which may contribute to the appearance of steatosis in dengue-infected patients. The interaction between GAPDH and full-length NS3 or its helicase domain in vitro as well as in NS3-transfected cells resulted in decreased GAPDH glycolytic activity. Reduced GAPDH glycolytic activity may lead to the accumulation of metabolic intermediates, shifting metabolism to alternative, non-glycolytic pathways. This report is the first to identify the interaction of the DENV2 NS3 protein with the GAPDH protein and to demonstrate that this interaction may play an important role in the molecular mechanism that triggers hepatic alterations

A Stillborn Multiple Organs’ Investigation from a Maternal DENV-4 Infection: Histopathological and Inflammatory Mediators Characterization

Dengue virus (DENV) is an emerging virus involved in outbreaks in Brazil. The association between the virus and vertical transmission, with disorders in the placenta, has raised a worldwide concern. On the 29th gestational week, a pregnant woman presented severe complications due to a DENV infection leading to maternal and fetus death. Postmortem analysis of fetal organs demonstrated the presence of DENV using reverse transcriptase polymerase chain reaction (RT-PCR) in the fetal brain and DENV non-structural protein 3 (NS3) staining in placenta and several peripheral fetal tissues, such as the brain, liver, lungs, and spleen. Histological analysis of the placenta and fetal organs revealed different types of tissue abnormalities, which included inflammation, hemorrhage, edema, and necrosis in placenta and tissue disorganization in the fetus, such as spongiform parenchyma, microglial inflammation, steatosis, hyalinose arteriolar, inflammatory cells in the alveolar septa, and disorganization of the lymphoid follicle. Increased cellularity (macrophage, Hofbauer cells and TCD8+ lymphocytes) and up-regulation of inflammatory mediators such as IFN-γ, TNF-α, RANTES/CCL5, MCP1/CCL2, and VEGF/R2 were detected in the liver, lung, spleen, brain, and placenta, supporting placental and fetus peripheral tissues inflammation. Maternal infection leading to the production of those vascular mediators may alter the vascular permeability, facilitating the virus entry and tissue and barrier dysfunction

Renal Injury in DENV-4 Fatal Cases: Viremia, Immune Response and Cytokine Profile.

Dengue virus (DENV) infections may result in asymptomatic cases or evolve into a severe disease, which involves multiple organ failure. Renal involvement in dengue can be potentially related to an increased mortality. Aiming to better understand the role of DENV in renal injury observed in human fatal cases, post-mortem investigations were performed in four DENV-4 renal autopsies during dengue epidemics in Brazil. Tissues were submitted to histopathology, immunohistochemistry, viral quantification, and characterization of cytokines and inflammatory mediators. Probably due the high viral load, several lesions were observed in the renal tissue, such as diffuse mononuclear infiltration around the glomerulus in the cortical region and in the medullary vessels, hyalinosis arteriolar, lymphocytic infiltrate, increased capsular fibrosis, proximal convoluted tubule (PCT) damage, edema, PCT debris formation, and thickening of the basal vessel membrane. These changes were associated with DENV-4 infection, as confirmed by the presence of DENV-specific NS3 protein, indicative of viral replication. The exacerbated presence of mononuclear cells at several renal tissue sites culminated in the secretion of proinflammatory cytokines and chemokines. Moreover, it can be suggested that the renal tissue injury observed here may have been due to the combination of both high viral load and exacerbated host immune response