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1.
World Neurosurg ; 133: 10-13, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31550543

RESUMO

BACKGROUND: Epstein-Barr virus (EBV)-positive diffuse large B-cell lymphoma (DLBCL) in an immunocompromised patient with organ transplantation demonstrated unusual brain magnetic resonance imaging (MRI) findings. Recognition of EBV-positive DLBCL by radiologists on MRI may prevent unnecessary neurosurgical resection, and it could be important to obtain viable cells for accurate diagnosis on stereotactic biopsy because of extensive necrosis. CASE DESCRIPTION: A 62-year-old woman presented to the emergency department with left hemiparesis grade III and dysarthria lasting for 3 weeks. She underwent kidney transplantation in 2007 and was taking immunosuppressants and had hypothyroidism. Brain MRI showed a 3.8-cm peripheral enhancing lesion with extensive central necrosis in association with marked perilesional edema. The irregular ringlike enhancing lesion showed diffusion restriction and mildly increased regional cerebral blood volume in the rim portion of the mass. 11C-Methionine positron emission tomography revealed slightly increased uptake in the peripheral lesion. The provisional diagnosis was a high-grade glioma. Stereotactic multiple biopsies were performed for the central necrotic area and peripheral enhancing lesion. The nonenhancing areas showed only necrotic material, without viable cells, and the enhancing portion showed viable cells for an accurate diagnosis in a frozen biopsy specimen. The pathologic diagnosis was EBV-positive DLBCL with extensive necrosis. Positron emission tomography of the chest, abdomen, pelvis, and neck soft tissues ruled out systemic diseases. She underwent whole-brain radiotherapy at a dose of 30.6 Gy. Eight months later, her neurologic symptoms had improved, with a stable brain lesion and improved perilesional edema. CONCLUSIONS: We report an immunocompromised patient with EBV-positive DLBCL, which showed atypical MRI findings, including extensive necrosis. Multiple biopsies were required for final diagnosis.


Assuntos
Encéfalo/patologia , Infecções por Vírus Epstein-Barr/patologia , Linfoma Difuso de Grandes Células B/patologia , Biópsia , Encéfalo/diagnóstico por imagem , Encéfalo/virologia , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/diagnóstico por imagem , Feminino , Humanos , Hospedeiro Imunocomprometido , Transplante de Rim , Linfoma Difuso de Grandes Células B/complicações , Linfoma Difuso de Grandes Células B/diagnóstico por imagem , Imagem por Ressonância Magnética , Pessoa de Meia-Idade , Necrose/diagnóstico por imagem , Necrose/patologia , Necrose/virologia , Transplantados
2.
Medicine (Baltimore) ; 98(44): e17797, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31689857

RESUMO

RATIONALE: Acute necrotizing encephalopathy (ANE) is a rapidly progressing disease associated with frequent neurologic sequelae and has poor prognosis. Currently, the diagnosis and treatment of ANE rely on neuroradiologic findings and offering supportive care. Here, we report the successful treatment of a teenager diagnosed with ANE using combination of high-dose methylprednisolone and oseltamivir. PATIENT CONCERNS: The patient, a 15-year-old female, presented with impaired consciousness and seizures secondary to acute upper respiratory tract infection. A series of brain magnetic resonance images (MRIs) were obtained toward establishing a possible diagnosis. DIAGNOSIS: Based on the history of presenting illness and subsequent brain MRI scans, the patient was diagnosed to be suffering from ANE. INTERVENTIONS: Following the diagnosis, the patient was placed on therapy comprising of high-dose methylprednisolone and oseltamivir. OUTCOMES: After treatment with methylprednisolone and oseltamivir for 15 days, the patient recovered nearly completely from ANE as confirmed by subsequent brain MRI scans. No complications or other emerging clinical symptoms were noted for the duration of follow-up that lasted 6 months. LESSONS: Contrary to common reports, ANE can occur beyond pediatric populations and its treatment should not be restricted to supportive care. Our case suggests that the use of high-dose corticosteroids and oseltamivir leads to promising prognosis.


Assuntos
Encéfalo/diagnóstico por imagem , Encefalite Viral/diagnóstico por imagem , Imagem por Ressonância Magnética/métodos , Infecções Respiratórias/complicações , Convulsões/diagnóstico por imagem , Adolescente , Corticosteroides/uso terapêutico , Antivirais/uso terapêutico , Encéfalo/patologia , Encéfalo/virologia , China , Encefalite Viral/tratamento farmacológico , Encefalite Viral/virologia , Feminino , Humanos , Necrose/diagnóstico por imagem , Necrose/virologia , Oseltamivir/uso terapêutico , Prognóstico , Infecções Respiratórias/virologia , Convulsões/patologia , Convulsões/virologia
3.
An Bras Dermatol ; 94(4): 446-448, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31644618

RESUMO

Necrolytic acral erythema is a distinct erythema that has been described as an extrahepatic manifestation of hepatitis C virus infection. Most reported cases have been in Africa, especially Egypt. We report the first case (to the best of our knowledge) of necrolytic acral erythema in a Chinese patient with HCV and HBV coinfection. We aim to increase awareness for recognizing this condition in the Chinese population.


Assuntos
Coinfecção/complicações , Eritema/patologia , Eritema/virologia , Hepatite B/complicações , Hepatite C/complicações , Adulto , China , Coinfecção/patologia , Extremidades/patologia , Hepatite B/patologia , Hepatite C/patologia , Humanos , Masculino , Necrose/virologia
4.
An. bras. dermatol ; 94(4): 446-448, July-Aug. 2019. graf
Artigo em Inglês | LILACS | ID: biblio-1038296

RESUMO

Abstract: Necrolytic acral erythema is a distinct erythema that has been described as an extrahepatic manifestation of hepatitis C virus infection. Most reported cases have been in Africa, especially Egypt. We report the first case (to the best of our knowledge) of necrolytic acral erythema in a Chinese patient with HCV and HBV coinfection. We aim to increase awareness for recognizing this condition in the Chinese population.


Assuntos
Humanos , Masculino , Adulto , Hepatite C/complicações , Eritema/patologia , Eritema/virologia , Coinfecção/complicações , Hepatite B/complicações , China , Hepatite C/patologia , Extremidades/patologia , Coinfecção/patologia , Hepatite B/patologia , Necrose/virologia
5.
Transbound Emerg Dis ; 66(5): 2033-2044, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31131546

RESUMO

Since December 2017, an infectious disease has caused economic hardship for duck farms and breeding ducks in many regions of China. This disease characterized by spleen necrosis and swelling, is due to a variant strain of duck orthoreovirus (DRV) (Duck/N-DRV-XT18/China/2018), which we isolated from the spleen of diseased ducks. After isolating the virus, we used next-generation sequencing technology to determine the entire genomic of the virus. Our phylogenetic analysis of 10 genomic segments showed that the N-DRV-XT18 strain is closely related to orthoreovirus isolates derived from ducks and geese, with nucleotide sequence identities for 10 genomic fragments ranging between 49.8% and 99.3%. In contract, the nucleotide sequence of N-DRV-XT18 genomic fragments are only 38.6% to 78.8% similar to the chicken orthoreovirus isolate. Therefore, we determined that this pathogen, causing duck spleen necrosis, is a new variant of a duck orthoreovirus that is significantly different from any previously reported waterfowl-derived othoreovirus.


Assuntos
Patos/virologia , Necrose/virologia , Orthoreovirus Aviário/isolamento & purificação , Doenças das Aves Domésticas/virologia , Baço/virologia , Animais , Sequência de Bases , Pequim , China , Sequenciamento de Nucleotídeos em Larga Escala , Necrose/etiologia , Filogenia , Infecções por Reoviridae/veterinária , Análise de Sequência de DNA , Sequenciamento Completo do Genoma
6.
Biomed Res Int ; 2019: 2121357, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31080811

RESUMO

Background: cIAP2 is involved in necroptosis as a key upstream regulation factor. We aimed to investigate the role of cIAP2 in ARDS/ALI induced by H7N9 virus through regulating the RIPK1/3 necroptosis pathway. Methods: Lung tissues of 11 patients who died from ARDS-complicated H7N9 infection between 2013 and 2016 were obtained as the H7N9-ARDS group. Lung tissues near benign lung nodules were acquired as the control group. Histological changes were evaluated by H&E staining. Protein levels of cIAP2, RIPK1, RIPK3, p-RIPK3, MLKL, and p-MLKL in the lung tissues were detected by Western Blot. The mRNA levels of cIAP2, RIPK1, and RIPK3 were detected by real-time PCR. Results: H7N9 virus infection had a high mortality, with ARDS being the leading cause of death. The protein level of cIAP2 in the experimental group was lower than that in the control group (P<0.05). However, the experimental group showed higher RIPK1, RIPK3, and p-RIPK3 protein levels than the control group (P<0.05), as well as the expression level of MLKL and p-MLKL protein, which is a key downstream protein in necroptosis (P<0.05). Conclusion: In tissues from patients with fatal H7N9, downregulation of cIAP2 and induction of necroptosis was observed. We could speculate that necroptosis of the pulmonary epithelium is associated with severe H7N9 infection leading to ARDS. Thus, necroptosis inhibition may be a novel therapy for H7N9 influenza virus.


Assuntos
Proteína 3 com Repetições IAP de Baculovírus/metabolismo , Subtipo H7N9 do Vírus da Influenza A/patogenicidade , Síndrome do Desconforto Respiratório do Adulto/metabolismo , Síndrome do Desconforto Respiratório do Adulto/virologia , Adulto , Idoso , Animais , Células Cultivadas , Regulação para Baixo/fisiologia , Feminino , Humanos , Pulmão/metabolismo , Pulmão/virologia , Masculino , Camundongos , Pessoa de Meia-Idade , Necrose/metabolismo , Necrose/virologia , Mucosa Respiratória/metabolismo , Mucosa Respiratória/virologia
9.
Vet Microbiol ; 227: 69-77, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30473354

RESUMO

A severe infectious disease characterized by nephritis, hepatitis and splenitis has attacked goslings around Shandong province in China since 2016. A novel chicken-origin avian orthoreovirus (ARV) was isolated with LMH cells from affected goslings named Reo/Goose/SDPY/1116/17 (SDPY-ARV) strain, and the infection was successfully reproduced experimentally. The ARV-SDPY full genome sequencing was conducted using Next-Generation Sequencing (NGS) technique on Illumina HiSeq platform. The complete genome of SDPY-ARV was 23,427 bp in length and consist of 10 dsRNA segments ranged from 1192 bp (S4) to 3958 bp (L1) which encoding 12 viral proteins. Genomic sequence analysis showed that the SDPY-ARV strain is in the same branch with broiler, pheasant-origin ARV isolates, and shares 51.8-96.2% of nucleotide identity of σC gene with them; while only 49.3-50.3% with waterfowl isolates. In addition, the occurrence of 10 segments genetic reassortment of SDPY strain is confirmed among the PA15511, the 1733 and the PA13649 strains from America. In conclusion, the causative agent of gosling hemorrhagic necrotic hepatitis and nephritis occurring in China is a novel chicken-origin goose orthoreovirus.


Assuntos
Gansos/virologia , Genoma Viral , Hepatite Viral Animal/etiologia , Orthoreovirus Aviário/genética , Orthoreovirus Aviário/isolamento & purificação , Doenças das Aves Domésticas/virologia , Infecções por Reoviridae/veterinária , Fatores Etários , Animais , Galinhas , China/epidemiologia , Genômica , Hepatite Viral Animal/epidemiologia , Hepatite Viral Animal/virologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Fígado/patologia , Fígado/virologia , Necrose/veterinária , Necrose/virologia , Fases de Leitura Aberta , Orthoreovirus Aviário/fisiologia , Filogenia , Doenças das Aves Domésticas/epidemiologia , Doenças das Aves Domésticas/transmissão , Infecções por Reoviridae/epidemiologia , Infecções por Reoviridae/transmissão , Infecções por Reoviridae/virologia , Análise de Sequência de DNA , Proteínas Virais/genética
10.
PLoS One ; 13(9): e0203853, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30204797

RESUMO

Cases of vomiting and diarrhoea were reported in racing pigeons in Western Australia in May, 2016. Morbidity and mortality rates were high. Similar clinical disease was seen in Victoria in December and by early 2017 had been reported in all states except the Northern Territory, in different classes of domestic pigeon-racing, fancy and meat bird-and in a flock of feral pigeons. Autopsy findings were frequently unremarkable; histological examination demonstrated significant hepatic necrosis as the major and consistent lesion, often with minimal inflammatory infiltration. Negative contrast tissue suspension and thin section transmission electron microscopy of liver demonstrated virus particles consistent with a member of the Reoviridae. Inoculation of trypsin-treated Vero, MDBK and MA-104 cell lines resulted in cytopathic changes at two days after infection. Next generation sequencing was undertaken using fresh liver samples and a previously undescribed group A rotavirus (genotype G18P[17]) of avian origin was identified and the virus was isolated in several cell lines. A q-RT-PCR assay was developed and used to screen a wider range of samples, including recovered birds. Episodes of disease have continued to occur and to reoccur in previously recovered lofts, with variable virulence reported. This is the first report of a rotavirus associated with hepatic necrosis in any avian species.


Assuntos
Doenças das Aves/virologia , Columbidae/virologia , Hepatopatias/veterinária , Infecções por Rotavirus/veterinária , Rotavirus , Animais , Austrália , Doenças das Aves/patologia , Bovinos , Diarreia/patologia , Diarreia/veterinária , Diarreia/virologia , Fígado/virologia , Hepatopatias/patologia , Hepatopatias/virologia , Necrose/patologia , Necrose/veterinária , Necrose/virologia , Infecções por Rotavirus/patologia , Células Vero , Vômito/patologia , Vômito/veterinária , Vômito/virologia
11.
Viruses ; 10(10)2018 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-30241284

RESUMO

In the 2014⁻2016 West Africa Ebola Virus (EBOV) outbreak, there was a significant concern raised about the potential for secondary bacterial infection originating from the gastrointestinal tract, which led to the empiric treatment of many patients with antibiotics. This retrospective pathology case series summarizes the gastrointestinal pathology observed in control animals in the rhesus EBOV-Kikwit intramuscular 1000 plaque forming unit infection model. All 31 Non-human primates (NHPs) exhibited lymphoid depletion of gut-associated lymphoid tissue (GALT) but the severity and the specific location of the depletion varied. Mesenteric lymphoid depletion and necrosis were present in 87% (27/31) of NHPs. There was mucosal barrier disruption of the intestinal tract with mucosal necrosis and/or ulceration most notably in the duodenum (16%), cecum (16%), and colon (29%). In the intestinal tract, hemorrhage was noted most frequently in the duodenum (52%) and colon (45%). There were focal areas of bacterial submucosal invasion in the gastrointestinal (GI) tract in 9/31 (29%) of NHPs. Only 2/31 (6%) had evidence of pancreatic necrosis. One NHP (3%) experienced jejunal intussusception which may have been directly related to EBOV. Immunofluorescence assays demonstrated EBOV antigen in CD68+ macrophage/monocytes and endothelial cells in areas of GI vascular injury or necrosis.


Assuntos
Ebolavirus/imunologia , Trato Gastrointestinal/patologia , Doença pelo Vírus Ebola/patologia , Animais , Antígenos CD/imunologia , Antígenos de Diferenciação Mielomonocítica/imunologia , Antígenos Virais/imunologia , Estudos de Coortes , Modelos Animais de Doenças , Feminino , Hemorragia Gastrointestinal/patologia , Hemorragia Gastrointestinal/virologia , Trato Gastrointestinal/virologia , Humanos , Tecido Linfoide/patologia , Tecido Linfoide/virologia , Macaca mulatta , Masculino , Necrose/patologia , Necrose/virologia , Estudos Retrospectivos
12.
Sci Rep ; 8(1): 14166, 2018 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-30242250

RESUMO

Respiratory syncytial virus (RSV) is a major cause of diseases of the respiratory tract in young children and babies, being mainly associated with bronchiolitis. RSV infection occurs primarily in pulmonary epithelial cells and, once infection is established, an immune response is triggered and neutrophils are recruited. In this study, we investigated the mechanisms underlying NET production induced by RSV. We show that RSV induced the classical ROS-dependent NETosis in human neutrophils and that RSV was trapped in DNA lattices coated with NE and MPO. NETosis induction by RSV was dependent on signaling by PI3K/AKT, ERK and p38 MAPK and required histone citrullination by PAD-4. In addition, RIPK1, RIPK3 and MLKL were essential to RSV-induced NETosis. MLKL was also necessary to neutrophil necrosis triggered by the virus, likely promoting membrane-disrupting pores, leading to neutrophil lysis and NET extrusion. Finally, we found that RSV infection of alveolar epithelial cells or lung fibroblasts triggers NET-DNA release by neutrophils, indicating that neutrophils can identify RSV-infected cells and respond to them by releasing NETs. The identification of the mechanisms responsible to mediate RSV-induced NETosis may prove valuable to the design of new therapeutic approaches to treat the inflammatory consequences of RSV bronchiolitis in young children.


Assuntos
Armadilhas Extracelulares/metabolismo , Necrose/metabolismo , Neutrófilos/metabolismo , Desiminases de Arginina em Proteínas/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Infecções por Vírus Respiratório Sincicial/metabolismo , Vírus Sincicial Respiratório Humano/patogenicidade , Adulto , Células Epiteliais Alveolares/metabolismo , Células Epiteliais Alveolares/virologia , Animais , Apoptose/fisiologia , Bronquiolite/metabolismo , Bronquiolite/virologia , Linhagem Celular , Armadilhas Extracelulares/virologia , Feminino , Humanos , Pulmão/metabolismo , Pulmão/virologia , Masculino , Necrose/virologia , Neutrófilos/virologia , Fosfatidilinositol 3-Quinases/metabolismo , Infecções por Vírus Respiratório Sincicial/virologia , Transdução de Sinais/fisiologia , Células Vero
13.
Plant Dis ; 102(11): 2268-2276, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30189158

RESUMO

Worldwide, Cucumber mosaic virus (CMV) is the causal agent of many economically important diseases. Based on immunological or molecular analysis, three distinct subgroups of CMV isolates can be identified (IA, IB, and II). In addition, some CMV isolates are associated with satellite RNAs (satRNAs), a type of noncoding transcript that may alter the symptoms of CMV infections. This study presents an analysis of CMV isolates occurring in legumes in Greece in respect to their genetic diversity, and the presence and diversity of their satRNA. Phylogenetic analysis of the CMV coat protein sequence of 18 legume and 5 tomato CMV isolates collected throughout Greece classified them within subgroups IA and IB, with a limited genetic diversity. The CMV satRNAs found in nine field legumes exhibiting mild symptoms and in one tomato with a necrotic syndrome contained a functional necrogenic motif; therefore, they were grouped within the necrogenic group of CMV-satRNAs. The necrotic phenotype was expressed in all legume CMV isolates containing necrogenic satRNAs when mechanically inoculated onto tomato plants. To our knowledge, this is the first observation that legumes host necrogenic CMV-satRNAs. The possible role of legumes in the epidemiology of CMV and necrogenic satRNA complex is discussed.


Assuntos
Satélite do Vírus do Mosaico do Pepino/genética , Cucumovirus/genética , Fabaceae/virologia , Variação Genética , Lycopersicon esculentum/virologia , Doenças das Plantas/virologia , Satélite do Vírus do Mosaico do Pepino/isolamento & purificação , Cucumovirus/isolamento & purificação , Necrose/virologia , Fenótipo , Filogenia , Alinhamento de Sequência
14.
Cell Death Dis ; 9(9): 904, 2018 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-30185776

RESUMO

The molecular mechanisms underlying the severe lung pathology that occurs during SARS-CoV infections remain incompletely understood. The largest of the SARS-CoV accessory protein open reading frames (SARS 3a) oligomerizes, dynamically inserting into late endosomal, lysosomal, and trans-Golgi-network membranes. While previously implicated in a non-inflammatory apoptotic cell death pathway, here we extend the range of SARS 3a pathophysiologic targets by examining its effects on necrotic cell death pathways. We show that SARS 3a interacts with Receptor Interacting Protein 3 (Rip3), which augments the oligomerization of SARS 3a helping drive necrotic cell death. In addition, by inserting into lysosomal membranes SARS 3a triggers lysosomal damage and dysfunction. Consequently, Transcription Factor EB (TFEB) translocates to the nucleus increasing the transcription of autophagy- and lysosome-related genes. Finally, SARS 3a activates caspase-1 either directly or via an enhanced potassium efflux, which triggers NLRP3 inflammasome assembly. In summary, Rip3-mediated oligomerization of SARS 3a causes necrotic cell death, lysosomal damage, and caspase-1 activation-all likely contributing to the clinical manifestations of SARS-CoV infection.


Assuntos
Necrose/virologia , Fases de Leitura Aberta/genética , Vírus da SARS/genética , Vírus da SARS/patogenicidade , Síndrome Respiratória Aguda Grave/patologia , Células A549 , Apoptose/fisiologia , Autofagia/fisiologia , Linhagem Celular , Linhagem Celular Tumoral , Células HEK293 , Células HeLa , Humanos , Inflamassomos/metabolismo , Membranas Intracelulares/patologia , Membranas Intracelulares/virologia , Lisossomos/metabolismo , Lisossomos/patologia , Lisossomos/virologia , Necrose/metabolismo , Necrose/patologia , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Síndrome Respiratória Aguda Grave/virologia
15.
PLoS Pathog ; 14(8): e1007235, 2018 08.
Artigo em Inglês | MEDLINE | ID: mdl-30075026

RESUMO

During Coxsackievirus B3 (CVB3) infection hepatitis is a potentially life threatening complication, particularly in newborns. Studies with type I interferon (IFN-I) receptor (IFNAR)-deficient mice revealed a key role of the IFN-I axis in the protection against CVB3 infection, whereas the source of IFN-I and cell types that have to be IFNAR triggered in order to promote survival are still unknown. We found that CVB3 infected IFN-ß reporter mice showed effective reporter induction, especially in hepatocytes and only to a minor extent in liver-resident macrophages. Accordingly, upon in vitro CVB3 infection of primary hepatocytes from murine or human origin abundant IFN-ß responses were induced. To identify sites of IFNAR-triggering we performed experiments with Mx reporter mice, which upon CVB3 infection showed massive luciferase induction in the liver. Immunohistological studies revealed that during CVB3 infection MX1 expression of hepatocytes was induced primarily by IFNAR-, and not by IFN-III receptor (IFNLR)-triggering. CVB3 infection studies with primary human hepatocytes, in which either the IFN-I or the IFN-III axis was inhibited, also indicated that primarily IFNAR-, and to a lesser extent IFNLR-triggering was needed for ISG induction. Interestingly, CVB3 infected mice with a hepatocyte-specific IFNAR ablation showed severe liver cell necrosis and ubiquitous viral dissemination that resulted in lethal disease, as similarly detected in classical IFNAR-/- mice. In conclusion, we found that during CVB3 infection hepatocytes are major IFN-I producers and that the liver is also the organ that shows strong IFNAR-triggering. Importantly, hepatocytes need to be IFNAR-triggered in order to prevent virus dissemination and to assure survival. These data are compatible with the hypothesis that during CVB3 infection hepatocytes serve as important IFN-I producers and sensors not only in the murine, but also in the human system.


Assuntos
Infecções por Coxsackievirus , Enterovirus Humano B/imunologia , Hepatócitos/metabolismo , Interferon beta/genética , Fígado/patologia , Receptor de Interferon alfa e beta/metabolismo , Animais , Células Cultivadas , Infecções por Coxsackievirus/complicações , Infecções por Coxsackievirus/genética , Infecções por Coxsackievirus/imunologia , Infecções por Coxsackievirus/virologia , Enterovirus Humano B/crescimento & desenvolvimento , Humanos , Interferon beta/metabolismo , Fígado/virologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Necrose/virologia , Receptor de Interferon alfa e beta/genética , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Células Vero , Carga Viral/genética , Carga Viral/imunologia
16.
Gynecol Obstet Invest ; 83(3): 259-267, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29621771

RESUMO

BACKGROUND/AIM: The aim of this study was to assess the functions of the necroptosis process on the prognosis of high-risk human papillomavirus (HR-HPV)-related cervical cancer. METHODS: PCR and western blotting were used to demonstrate the expression of the necroptosis marker, mixed lineage kinase domain-like protein (MLKL), in whole blood and peripheral blood mononuclears (PBMCs) of 89 cervical cancer patients and 15 healthy volunteers. Necroptosis levels and M1 polarization were determined in tumor co-cultured macrophages. RESULTS: We found that MLKL expressions were significantly increased in cervical cancer patients in both whole blood and PBMC samples compared to the expressions in the healthy controls. Low MLKL expression was significantly associated with decreased survival rate in overall survival and disease-free survival. Co-culture cervical cancer cells decrease the necroptosis process of macrophage, together with the proinflammatory factors (M1 markers) downregulation, and this negative regulation was exacerbated in HPV-positive cases. Necroptosis enhancer RIPK3 overexpression showed reversed regulation of these M1 markers, suggesting that co-culture cervical cancer cells decrease the macrophage M1 polarization partly through necroptosis downregulation. CONCLUSION: Our study revealed that necroptosis process could be a relevant marker for the determination of the prognosis in cervical cancer patients, which might be because of its role in regulating macrophage polarization.


Assuntos
Apoptose/fisiologia , Polaridade Celular , Macrófagos/virologia , Papillomaviridae , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Estudos de Casos e Controles , Regulação para Baixo , Feminino , Humanos , Leucócitos Mononucleares/virologia , Macrófagos/patologia , Pessoa de Meia-Idade , Necrose/virologia , Prognóstico , Proteínas Quinases/sangue , Proteína Serina-Treonina Quinases de Interação com Receptores/sangue , Resultado do Tratamento
18.
Front Immunol ; 9: 2935, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30619295

RESUMO

Background: Fulminant hepatitis (FH) is a serious threat to human life, accompanied by massive and rapid necroinflammation. Kupffer cells, the major immune cell population involved in innate immune responses, are considered to be central for FH. Fibrinogen-like protein 2 (Fgl2) is a pro-coagulant protein that is substantially induced in macrophages upon viral infection, and Fgl2 depletion represses murine hepatitis virus strain 3 (MHV-3) infection. Clara cell 10 kDa (CC10) protein is a secretory protein with anti-inflammatory properties in allergic rhinitis and asthma. However, its mechanisms of action and pathogenic roles in other disease are still unclear. In this study, we aimed to determine the role of CC10 in FH and the regulation of Fgl2 by CC10. Methods: A mouse FH model was established by peritoneal injection of MHV-3. The mice received CC10 protein through tail vein injection before viral infection. Survival rate, liver function, liver histology, fibrin deposition, and necrosis were examined. The regulatory effect of CC10 on Fgl2 expression was investigated using THP-1 cells and mouse peritoneal macrophages in vitro. Results: In the mouse FH model induced by MHV-3, the survival rate increased from 0 to 12.5% in the CC10 group compared to that in the saline-only control group. Meanwhile, the levels of ALT and AST in serum were significantly decreased and liver damage was reduced. Furthermore, hepatic Fgl2, TNF-α, and IL-1ß expression was obviously downregulated together with fibrin deposition, and hepatocyte apoptosis was reduced after administration of CC10 protein. In vitro, CC10 was found to significantly inhibit the expression of Fgl2 in IFN-γ-treated THP-1 cells and MHV-3-infected mouse peritoneal macrophages by western blot and real-time PCR. However, there was no direct interaction between CC10 and Fgl2 as shown by co-immunoprecipitation. Microarray investigations suggested that HMG-box transcription factor 1 (HBP1) was significantly low in CC10-treated and IFN-γ-primed THP-1 cells. HBP1-siRNA treatment abrogated the inhibitory effect of CC10 on Fgl2 expression in Human Umbilical Vein Endothelial cells (HUVECs). Conclusion:CC10 protects against MHV-3-induced FH via suppression of Fgl2 expression in macrophages. Such effects may be mediated by the transcription factor HBP1.


Assuntos
Infecções por Coronavirus/imunologia , Fibrinogênio/metabolismo , Hepatite Viral Animal/imunologia , Falência Hepática Aguda/imunologia , Uteroglobina/metabolismo , Animais , Células CHO , Infecções por Coronavirus/mortalidade , Infecções por Coronavirus/patologia , Infecções por Coronavirus/virologia , Cricetulus , Modelos Animais de Doenças , Feminino , Fibrinogênio/genética , Hepatite Viral Animal/mortalidade , Hepatite Viral Animal/patologia , Hepatite Viral Animal/virologia , Proteínas de Grupo de Alta Mobilidade/metabolismo , Células Endoteliais da Veia Umbilical Humana , Humanos , Fígado/imunologia , Fígado/patologia , Fígado/virologia , Falência Hepática Aguda/mortalidade , Falência Hepática Aguda/patologia , Falência Hepática Aguda/virologia , Macrófagos/imunologia , Macrófagos/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Vírus da Hepatite Murina/imunologia , Vírus da Hepatite Murina/patogenicidade , Necrose/imunologia , Necrose/patologia , Necrose/virologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismo , Proteínas Repressoras/metabolismo , Taxa de Sobrevida , Células THP-1 , Uteroglobina/genética
19.
Emerg Infect Dis ; 23(12): 1958-1965, 2017 12.
Artigo em Inglês | MEDLINE | ID: mdl-28841405

RESUMO

Wellfleet Bay virus (WFBV), a novel orthomyxovirus in the genus Quaranjavirus, was first isolated in 2006 from carcasses of common eider (Somateria mollissima) during a mortality event in Wellfleet Bay (Barnstable County, Massachusetts, USA) and has since been repeatedly isolated during recurrent mortality events in this location. Hepatic, pancreatic, splenic, and intestinal necrosis was observed in dead eiders. We inoculated 6-week-old common eider ducklings with WFBV in an attempt to recreate the naturally occurring disease. Approximately 25% of inoculated eiders had onset of clinical disease and required euthanasia; an additional 18.75% were adversely affected based on net weight loss during the trial. Control ducklings did not become infected and did not have clinical disease. Infected ducklings with clinical disease had pathologic lesions consistent with those observed during natural mortality events. WFBV was reisolated from 37.5% of the inoculated ducklings. Ducklings surviving to 5 days postinoculation developed serum antibody titers to WFBV.


Assuntos
Anticorpos Antivirais/biossíntese , Doenças das Aves/virologia , Patos/virologia , Necrose/veterinária , Infecções por Orthomyxoviridae/veterinária , Orthomyxoviridae/fisiologia , Animais , Baías , Doenças das Aves/imunologia , Doenças das Aves/patologia , Modelos Animais de Doenças , Patos/imunologia , Intestinos/imunologia , Intestinos/patologia , Intestinos/virologia , Fígado/imunologia , Fígado/patologia , Fígado/virologia , Massachusetts , Necrose/imunologia , Necrose/patologia , Necrose/virologia , Orthomyxoviridae/patogenicidade , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/patologia , Infecções por Orthomyxoviridae/virologia , Pâncreas/imunologia , Pâncreas/patologia , Pâncreas/virologia , Baço/imunologia , Baço/patologia , Baço/virologia , Perda de Peso
20.
J Immunol ; 198(11): 4513-4523, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28461570

RESUMO

Immunotherapeutic strategies for malignant glioma have to overcome the immunomodulatory activities of M2 monocytes that appear in the circulation and as tumor-associated macrophages (TAMs). M2 cell products contribute to the growth-promoting attributes of the tumor microenvironment (TME) and bias immunity toward type 2, away from the type 1 mechanisms with antitumor properties. To drive type 1 immunity in CNS tissues, we infected GL261 tumor-bearing mice with attenuated rabies virus (RABV). These neurotropic viruses spread to CNS tissues trans-axonally, where they induce a strong type 1 immune response that involves Th1, CD8, and B cell entry across the blood-brain barrier and virus clearance in the absence of overt sequelae. Intranasal infection with attenuated RABV prolonged the survival of mice bearing established GL261 brain tumors. Despite the failure of virus spread to the tumor, infection resulted in significantly enhanced tumor necrosis, extensive CD4 T cell accumulation, and high levels of the proinflammatory factors IFN-γ, TNF-α, and inducible NO synthase in the TME merely 4 d postinfection, before significant virus spread or the appearance of RABV-specific immune mechanisms in CNS tissues. Although the majority of infiltrating CD4 cells appeared functionally inactive, the proinflammatory changes in the TME later resulted in the loss of accumulating M2 and increased M1 TAMs. Mice deficient in the Th1 transcription factor T-bet did not gain any survival advantage from RABV infection, exhibiting only limited tumor necrosis and no change in TME cytokines or TAM phenotype and highlighting the importance of type 1 mechanisms in this process.


Assuntos
Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Encéfalo/virologia , Vírus da Raiva/imunologia , Microambiente Tumoral/imunologia , Animais , Linfócitos B/imunologia , Barreira Hematoencefálica/imunologia , Barreira Hematoencefálica/patologia , Barreira Hematoencefálica/virologia , Encéfalo/imunologia , Neoplasias Encefálicas/virologia , Linfócitos T CD4-Positivos , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Interferon gama/biossíntese , Interferon gama/imunologia , Camundongos , Necrose/virologia , Óxido Nítrico Sintase Tipo II/biossíntese , Óxido Nítrico Sintase Tipo II/metabolismo , Vírus da Raiva/genética , Vírus da Raiva/fisiologia , Proteínas com Domínio T/deficiência , Proteínas com Domínio T/metabolismo , Células Th2/imunologia , Fator de Necrose Tumoral alfa/biossíntese , Fator de Necrose Tumoral alfa/imunologia
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