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1.
Sci Rep ; 11(1): 1793, 2021 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-33469056

RESUMO

COVID-19 caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) and other respiratory viral (non-CoV-2-RV) infections are associated with thrombotic complications. The differences in prothrombotic potential between SARS-CoV-2 and non-CoV-2-RV have not been well characterised. We compared the thrombotic rates between these two groups of patients directly and further delved into their coagulation profiles. In this single-center, retrospective cohort study, all consecutive COVID-19 and non-CoV-2-RV patients admitted between January 15th and April 10th 2020 were included. Coagulation parameters studied were prothrombin time and activated partial thromboplastin time and its associated clot waveform analysis (CWA) parameter, min1, min2 and max2. In the COVID-19 (n = 181) group there were two (1.0 event/1000-hospital-days) myocardial infarction events while one (1.8 event/1000-hospital-day) was reported in the non-CoV-2-RV (n = 165) group. These events occurred in patients who were severely ill. There were no venous thrombotic events. Coagulation parameters did not differ throughout the course of mild COVID-19. However, CWA parameters were significantly higher in severe COVID-19 compared with mild disease, suggesting hypercoagulability (min1: 6.48%/s vs 5.05%/s, P < 0.001; min2: 0.92%/s2 vs 0.74%/s2, P = 0.033). In conclusion, the thrombotic rates were low and did not differ between COVID-19 and non-CoV-2-RV patients. The hypercoagulability in COVID-19 is a highly dynamic process with the highest risk occurring when patients were most severely ill. Such changes in haemostasis could be detected by CWA. In our population, a more individualized thromboprophylaxis approach, considering clinical and laboratory factors, is preferred over universal pharmacological thromboprophylaxis for all hospitalized COVID-19 patients and such personalized approach warrants further research.


Assuntos
/patologia , Trombofilia/diagnóstico , Viroses/patologia , Adulto , /virologia , Feminino , Humanos , Masculino , Infarto do Miocárdio/complicações , Infarto do Miocárdio/diagnóstico , Tempo de Tromboplastina Parcial , Tempo de Protrombina , Estudos Retrospectivos , Fatores de Risco , Índice de Gravidade de Doença , Trombofilia/complicações , Viroses/complicações
2.
Cells ; 9(11)2020 11 07.
Artigo em Inglês | MEDLINE | ID: mdl-33171736

RESUMO

Viruses exhibit an elegant simplicity, as they are so basic, but so frightening. Although only a few are life threatening, they have substantial implications for human health and the economy, as exemplified by the ongoing coronavirus pandemic. Viruses are rather small infectious agents found in all types of life forms, from animals and plants to prokaryotes and archaebacteria. They are obligate intracellular parasites, and as such, subvert many molecular and cellular processes of the host cell to ensure their own replication, amplification, and subsequent spread. This special issue addresses the cell biology of viral infections based on a collection of original research articles, communications, opinions, and reviews on various aspects of virus-host cell interactions. Together, these articles not only provide a glance into the latest research on the cell biology of viral infections, but also include novel technological developments.


Assuntos
Viroses/patologia , Animais , Betacoronavirus/fisiologia , Interações Hospedeiro-Patógeno , Humanos , Transdução de Sinais , Viroses/metabolismo , Viroses/virologia , Zika virus/fisiologia
3.
Proc Natl Acad Sci U S A ; 117(40): 24998-25007, 2020 10 06.
Artigo em Inglês | MEDLINE | ID: mdl-32958643

RESUMO

Infections elicit immune adaptations to enable pathogen resistance and/or tolerance and are associated with compositional shifts of the intestinal microbiome. However, a comprehensive understanding of how infections with pathogens that exhibit distinct capability to spread and/or persist differentially change the microbiome, the underlying mechanisms, and the relative contribution of individual commensal species to immune cell adaptations is still lacking. Here, we discovered that mouse infection with a fast-spreading and persistent (but not a slow-spreading acute) isolate of lymphocytic choriomeningitis virus induced large-scale microbiome shifts characterized by increased Verrucomicrobia and reduced Firmicute/Bacteroidetes ratio. Remarkably, the most profound microbiome changes occurred transiently after infection with the fast-spreading persistent isolate, were uncoupled from sustained viral loads, and were instead largely caused by CD8 T cell responses and/or CD8 T cell-induced anorexia. Among the taxa enriched by infection with the fast-spreading virus, Akkermansia muciniphila, broadly regarded as a beneficial commensal, bloomed upon starvation and in a CD8 T cell-dependent manner. Strikingly, oral administration of A. muciniphila suppressed selected effector features of CD8 T cells in the context of both infections. Our findings define unique microbiome differences after chronic versus acute viral infections and identify CD8 T cell responses and downstream anorexia as driver mechanisms of microbial dysbiosis after infection with a fast-spreading virus. Our data also highlight potential context-dependent effects of probiotics and suggest a model in which changes in host behavior and downstream microbiome dysbiosis may constitute a previously unrecognized negative feedback loop that contributes to CD8 T cell adaptations after infections with fast-spreading and/or persistent pathogens.


Assuntos
Anorexia/imunologia , Antígenos CD8/imunologia , Memória Imunológica/imunologia , Coriomeningite Linfocítica/imunologia , Viroses/imunologia , Animais , Anorexia/microbiologia , Anorexia/virologia , Antígenos CD8/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/microbiologia , Disbiose/imunologia , Disbiose/microbiologia , Disbiose/virologia , Firmicutes/imunologia , Firmicutes/metabolismo , Microbioma Gastrointestinal/imunologia , Humanos , Coriomeningite Linfocítica/microbiologia , Coriomeningite Linfocítica/patologia , Vírus da Coriomeningite Linfocítica/patogenicidade , Camundongos , Linfócitos T/imunologia , Linfócitos T/microbiologia , Verrucomicrobia/imunologia , Verrucomicrobia/patogenicidade , Viroses/microbiologia , Viroses/patologia
4.
Int J Mol Sci ; 21(13)2020 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-32630064

RESUMO

Vimentin is an intermediate filament protein that plays key roles in integration of cytoskeletal functions, and therefore in basic cellular processes such as cell division and migration. Consequently, vimentin has complex implications in pathophysiology. Vimentin is required for a proper immune response, but it can also act as an autoantigen in autoimmune diseases or as a damage signal. Although vimentin is a predominantly cytoplasmic protein, it can also appear at extracellular locations, either in a secreted form or at the surface of numerous cell types, often in relation to cell activation, inflammation, injury or senescence. Cell surface targeting of vimentin appears to associate with the occurrence of certain posttranslational modifications, such as phosphorylation and/or oxidative damage. At the cell surface, vimentin can act as a receptor for bacterial and viral pathogens. Indeed, vimentin has been shown to play important roles in virus attachment and entry of severe acute respiratory syndrome-related coronavirus (SARS-CoV), dengue and encephalitis viruses, among others. Moreover, the presence of vimentin in specific virus-targeted cells and its induction by proinflammatory cytokines and tissue damage contribute to its implication in viral infection. Here, we recapitulate some of the pathophysiological implications of vimentin, including the involvement of cell surface vimentin in interaction with pathogens, with a special focus on its role as a cellular receptor or co-receptor for viruses. In addition, we provide a perspective on approaches to target vimentin, including antibodies or chemical agents that could modulate these interactions to potentially interfere with viral pathogenesis, which could be useful when multi-target antiviral strategies are needed.


Assuntos
Vírus da SARS/fisiologia , Vimentina/metabolismo , Viroses/patologia , Anticorpos/imunologia , Anticorpos/metabolismo , Anticorpos/uso terapêutico , Betacoronavirus/isolamento & purificação , Infecções por Coronavirus/tratamento farmacológico , Interações Hospedeiro-Patógeno , Humanos , Pandemias , Pneumonia Viral/tratamento farmacológico , Bibliotecas de Moléculas Pequenas/química , Bibliotecas de Moléculas Pequenas/farmacologia , Bibliotecas de Moléculas Pequenas/uso terapêutico , Vimentina/química , Vimentina/imunologia , Viroses/tratamento farmacológico , Viroses/metabolismo , Replicação Viral/efeitos dos fármacos
5.
Adv Exp Med Biol ; 1207: 425-432, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32671765

RESUMO

Autophagy plays an important role in the fight against viral infection, which can directly remove the virus, interact with the viral protein, and at the same time regulate the innate and adaptive immunity and promote virus clearance. The virus has also evolved autophagy, which evades, antagonizes and utilizes autophagy, and regulates autophagy pathways, affects autophagy maturation, changes autophagy small body environment or changes the body's immune response type to promote or inhibit autophagy. This chapter introduces the possible mechanisms of autophagy during pathogen infection such as human immunodeficiency virus and hepatitis virus, in order to provide new methods for the prevention and treatment of viral infection.


Assuntos
Autofagia , Viroses , Imunidade Adaptativa , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunidade Inata , Viroses/imunologia , Viroses/patologia
6.
Cardiovasc Pathol ; 49: 107260, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32683240

RESUMO

PURPOSE: to study the effect of immunosupressive therapy (IST) in the virus-negative and virus-positive patients with immune-mediated myocarditis. METHODS: in 60 patients (45 male, 46.7 ± 11.8 years, mean LV EDD, 6.7 ± 0.7 cm, EF 26.2 ± 9.1%) active/borderline myocarditis was verified by endomyocardial biopsy (n = 38), intraoperative biopsy (n = 10), examination of explanted heart (n = 3) and autopsy (n = 9). Indications for IST determined based on histological, immune activity. The follow-up was 19.0 [7.25; 40.25] months. RESULTS: The viral genome in the myocardium was detected in 32 patients (V+ group), incl. parvovirus B19 in 23. The anti-heart antibody level was equally high in the V+ and V- patients. Antiviral therapy was administered in 24 patients. IST (in 22 V+ and 24 V- patients) include steroids (n = 40), hydroxychloroquine (n = 20), azathioprine (n = 21). The significant decrease of LV EDD (6.7 ± 0.7 to 6.4 ± 0.8), PAP (48.9 ± 15.5 to 39.4 ± 11.5 mm Hg, р<0,01), increase of EF (26.5 ± 0.9 to 36.0 ± 10.8), and lower lethality (23.9% and 64.3%; RR 0.37, 95% CI 0.19-0.71), p<0.01, were found only in IST group. Significant improvement due to IST were achieved not only in V-, but also in V+ patients. CONCLUSIONS: IST in patients with immune-mediated lymphocytic myocarditis is effective and is associated with lower lethality both in virus-negative and virus-positive patients.


Assuntos
Antivirais/uso terapêutico , Autoanticorpos/sangue , Imunossupressores/uso terapêutico , Linfócitos/efeitos dos fármacos , Miocardite/tratamento farmacológico , Miocárdio/imunologia , Viroses/tratamento farmacológico , Vírus/efeitos dos fármacos , Adulto , Idoso , Biópsia , Feminino , Interações Hospedeiro-Patógeno , Humanos , Linfócitos/imunologia , Linfócitos/patologia , Linfócitos/virologia , Masculino , Pessoa de Meia-Idade , Miocardite/imunologia , Miocardite/patologia , Miocardite/virologia , Miocárdio/patologia , Resultado do Tratamento , Viroses/imunologia , Viroses/patologia , Viroses/virologia , Vírus/imunologia , Adulto Jovem
7.
Int J Mol Sci ; 21(11)2020 Jun 08.
Artigo em Inglês | MEDLINE | ID: mdl-32521619

RESUMO

Viruses use cell machinery to replicate their genome and produce viral proteins. For this reason, several intracellular factors, including the redox state, might directly or indirectly affect the progression and outcome of viral infection. In physiological conditions, the redox balance between oxidant and antioxidant species is maintained by enzymatic and non-enzymatic systems, and it finely regulates several cell functions. Different viruses break this equilibrium and induce an oxidative stress that in turn facilitates specific steps of the virus lifecycle and activates an inflammatory response. In this context, many studies highlighted the importance of redox-sensitive pathways as novel cell-based targets for therapies aimed at blocking both viral replication and virus-induced inflammation. In the review, we discuss the most recent findings in this field. In particular, we describe the effects of natural or synthetic redox-modulating molecules in inhibiting DNA or RNA virus replication as well as inflammatory pathways. The importance of the antioxidant transcription factor Nrf2 is also discussed. Most of the data reported here are on influenza virus infection. We believe that this approach could be usefully applied to fight other acute respiratory viral infections characterized by a strong inflammatory response, like COVID-19.


Assuntos
Antivirais/uso terapêutico , Oxirredução/efeitos dos fármacos , Viroses/tratamento farmacológico , Animais , Infecções por Coronavirus/tratamento farmacológico , Glutationa/metabolismo , Humanos , Inflamação/tratamento farmacológico , Influenza Humana/tratamento farmacológico , Viroses/imunologia , Viroses/patologia , Replicação Viral/efeitos dos fármacos
9.
Influenza Other Respir Viruses ; 14(6): 739-746, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32567818

RESUMO

BACKGROUND: Acute respiratory illnesses are a leading cause of global morbidity and mortality in children. Coinfection with multiple respiratory viruses is common. Although the effects of each virus have been studied individually, the impacts of coinfection on disease severity are less understood. METHODS: A secondary analysis was performed of a maternal influenza vaccine trial conducted between 2011 and 2014 in Nepal. Prospective weekly household-based active surveillance of infants was conducted from birth to 180 days of age. Mid-nasal swabs were collected and tested for respiratory syncytial virus (RSV), rhinovirus, influenza, human metapneumovirus (HMPV), coronavirus, parainfluenza (HPIV), and bocavirus by RT-PCR. Coinfection was defined as the presence of two or more respiratory viruses detected as part of the same illness episode. RESULTS: Of 1730 infants with a respiratory illness, 327 (19%) had at least two respiratory viruses detected in their primary illness episode. Of 113 infants with influenza, 23 (20%) had coinfection. Of 214 infants with RSV, 87 (41%) had coinfection. The cohort of infants with coinfection had increased occurrence of fever lasting ≥ 4 days (OR 1.4, 95% CI: 1.1, 2.0), and so did the subset of coinfected infants with influenza (OR 5.8, 95% CI: 1.8, 18.7). Coinfection was not associated with seeking further care (OR 1.1, 95% CI: 0.8, 1.5) or pneumonia (OR 1.2, 95% CI: 0.96, 1.6). CONCLUSION: A high proportion of infants had multiple viruses detected. Coinfection was associated with greater odds of fever lasting for four or more days, but not with increased illness severity by other measures.


Assuntos
Coinfecção/epidemiologia , Coinfecção/virologia , Infecções Respiratórias/epidemiologia , Infecções Respiratórias/virologia , Coinfecção/patologia , Febre/epidemiologia , Febre/patologia , Febre/virologia , Humanos , Lactente , Recém-Nascido , Nepal/epidemiologia , Razão de Chances , Estudos Prospectivos , Infecções Respiratórias/patologia , População Rural , Viroses/epidemiologia , Viroses/patologia , Viroses/virologia , Vírus/classificação , Vírus/isolamento & purificação
11.
Medicine (Baltimore) ; 99(15): e19744, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32282734

RESUMO

RATIONALE: Tattooing is a procedure where ink is inserted typically in the intraepidermal space of the skin. Multiple incidences of viral infections following tattooing which lead to warts have been reported in recent years. The aim of this report was to show a relatively rare adverse effect after tattooing - verruca plana. PATIENT CONCERNS: A 27-year-old female presented to our department with complains of multiple verrucous papules over her 2-year-old tattoo without itch. DIAGNOSES: Pathological investigation confirmed the diagnosis as verruca plana. INTERVENTIONS: The patient was treated with 3 cycles of liquid nitrogen cryotherapy and 5% imiquimod cream for 5 months. OUTCOMES: A significant improvement in her lesions was observed after the combined treatment. LESSONS: Clinically, verruca plana post-tattooing is relatively less reported. We need to combine clinical manifestations with pathological results to arrive at a definitive diagnosis. Besides, there are a large numbers of post-tattoo complications and various routes of virus inoculation. Therefore, it is important for medical professionals to caution people before considering to have a tattoo.


Assuntos
Tatuagem/efeitos adversos , Viroses/complicações , Verrugas/patologia , Verrugas/terapia , Adjuvantes Imunológicos/administração & dosagem , Adjuvantes Imunológicos/uso terapêutico , Administração Tópica , Adulto , Terapia Combinada , Crioterapia/métodos , Feminino , Humanos , Imiquimode/administração & dosagem , Imiquimode/uso terapêutico , Resultado do Tratamento , Viroses/patologia , Verrugas/etiologia
12.
Clin Dermatol ; 38(1): 35-41, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32197747

RESUMO

A rash is a disseminated eruption of cutaneous lesions with great variation in appearance, cause, and severity. When the physician is facing a rash, the history and physical examination of the patient are extremely important for the identification of the disease and its causal agent. There are various causes for a rash, which may be infectious, allergic, or rheumatologic, besides many others. Rashes associated with mucosal ulcers may have causes related to viral and bacterial infections or drug reactions. They may be associated with measles; erythema infectiosum; roseola infantum; rubella; hand, foot, and mouth disease; pityriasis rosea; dengue fever; chikungunya; zika; scarlet fever; meningococcal diseases; syphilis; and exanthematous drug eruptions.


Assuntos
Infecções Bacterianas/complicações , Exantema/etiologia , Exantema/microbiologia , Membrana Mucosa/patologia , Úlcera/etiologia , Úlcera/microbiologia , Viroses/complicações , Infecções Bacterianas/patologia , Exantema/patologia , Humanos , Úlcera/patologia , Viroses/patologia
13.
Clin Exp Immunol ; 200(3): 215-227, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32201938

RESUMO

Capping protein regulator and myosin 1 linker 2 (CARMIL2) deficiency is characterized by impaired T cell activation, which is attributed to defective CD28-mediated co-signaling. Herein, we aimed to analyze the effect of exogenous interleukin (IL)-2 on in-vitro T cell activation and proliferation in a family with CARMIL2 deficiency. This study included four children (one male and three females; aged 2·5-10 years at presentation). The patients presented with inflammatory bowel disease and recurrent viral infections. Genetic analysis revealed a novel homozygous 25-base pairs deletion in CARMIL2. Immunoblotting demonstrated the absence of CARMIL2 protein in all four patients and confirmed the diagnosis of CARMIL2 deficiency. T cells were activated in-vitro with the addition of IL-2 in different concentrations. CD25 and interferon (IFN)-γ levels were measured after 48 h and 5 days of activation. CD25 surface expression on activated CD8+ and CD4+ T cells was significantly diminished in all patients compared to healthy controls. Additionally, CD8+ T cells from all patients demonstrated significantly reduced IFN-γ production. When cells derived from CARMIL2-deficient patients were treated with IL-2, CD25 and IFN-γ production increased in a dose-dependent manner. T cell proliferation, as measured by Cell Trace Violet, was impaired in one patient and it was also rescued with IL-2. In conclusion, we found that IL-2 rescued T cell activation and proliferation in CARMIL2-deficient patients. Thus, IL-2 should be further studied as a potential therapeutic modality for these patients.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Proliferação de Células/efeitos dos fármacos , Interleucina-2/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Proteínas dos Microfilamentos/deficiência , Mutação , Linfócitos T CD8-Positivos/patologia , Criança , Pré-Escolar , Feminino , Humanos , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/imunologia , Doenças Inflamatórias Intestinais/patologia , Ativação Linfocitária/genética , Masculino , Viroses/genética , Viroses/imunologia , Viroses/patologia
14.
Cell Host Microbe ; 27(3): 329-344, 2020 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-32164844

RESUMO

The intestine is an essential physical and immunological barrier comprised of a monolayer of diverse and specialized epithelial cells that perform functions ranging from nutrient absorption to pathogen sensing and intestinal homeostasis. The intestinal barrier prevents translocation of intestinal microbes into internal compartments. The microbiota is comprised of a complex community largely populated by diverse bacterial species that provide metabolites, nutrients, and immune stimuli that promote intestinal and organismal health. Although commensal organisms promote health, enteric pathogens, including a diverse plethora of enteric viruses, cause acute and chronic diseases. The barrier epithelium plays fundamental roles in immune defenses against enteric viral infections by integrating diverse signals, including those from the microbiota, to prevent disease. Importantly, many model systems have contributed to our understanding of this complex interface. This review will focus on the antiviral mechanisms at play within the intestinal epithelium and how these responses are shaped by the microbiota.


Assuntos
Microbioma Gastrointestinal , Enteropatias/virologia , Mucosa Intestinal/microbiologia , Viroses/patologia , Animais , Caenorhabditis elegans/microbiologia , Caenorhabditis elegans/virologia , Culicidae/imunologia , Culicidae/virologia , Drosophila melanogaster/imunologia , Drosophila melanogaster/virologia , Humanos , Imunidade Inata , Camundongos , Viroses/microbiologia
15.
Nat Commun ; 11(1): 1288, 2020 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-32152316

RESUMO

Co-inhibitory pathways have a fundamental function in regulating T cell responses and control the balance between promoting efficient effector functions and restricting immune pathology. The TIGIT pathway has been implicated in promoting T cell dysfunction in chronic viral infection. Importantly, TIGIT signaling is functionally linked to IL-10 expression, which has an effect on both virus control and maintenance of tissue homeostasis. However, whether TIGIT has a function in viral persistence or limiting tissue pathology is unclear. Here we report that TIGIT modulation effectively alters the phenotype and cytokine profile of T cells during influenza and chronic LCMV infection, but does not affect virus control in vivo. Instead, TIGIT has an important effect in limiting immune pathology in peripheral organs by inducing IL-10. Our data therefore identify a function of TIGIT in limiting immune pathology that is independent of viral clearance.


Assuntos
Receptores Imunológicos/metabolismo , Viroses/imunologia , Viroses/patologia , Doença Aguda , Animais , Linfócitos T CD8-Positivos/imunologia , Doença Crônica , Citocinas/metabolismo , Mediadores da Inflamação/metabolismo , Interleucina-10/biossíntese , Fígado/patologia , Fígado/virologia , Pulmão/irrigação sanguínea , Pulmão/patologia , Vírus da Coriomeningite Linfocítica/fisiologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Infecções por Orthomyxoviridae/imunologia , Infecções por Orthomyxoviridae/patologia , Baço/imunologia
16.
BMC Med Genet ; 21(1): 61, 2020 03 27.
Artigo em Inglês | MEDLINE | ID: mdl-32216767

RESUMO

BACKGROUND: Wolcott-Rallison Syndrome (WRS) is a rare autosomal recessive disease that is the most common cause of neonatal diabetes in consanguineous families. WRS is caused by various genetic alterations of the Eukaryotic Translation Initiation Factor 2-Alpha Kinase 3 (EIF2AK3) gene. METHODS: Genetic analysis of a consanguineous family where two children were diagnosed with WRS was performed by Sanger sequencing. The altered protein was investigated by in vitro cloning, expression and immunohistochemistry. RESULTS: The first cases in Hungary, - two patients in one family, where the parents were fourth-degree cousins - showed the typical clinical features of WRS: early onset diabetes mellitus with hyperglycemia, growth retardation, infection-induced multiple organ failure. The genetic background of the disease was a novel alteration in the EIF2AK3 gene involving the splice site of exon 11- intron 11-12 boundary: g.53051_53062delinsTG. According to cDNA sequencing this created a new splice site and resulted in a frameshift and the development of an early termination codon at amino acid position 633 (p.Pro627AspfsTer7). Based on in vitro cloning and expression studies, the truncated protein was functionally inactive. Immunohistochemistry revealed that the intact protein was absent in the islets of pancreas, furthermore insulin expressing cells were also dramatically diminished. Elevated GRP78 and reduced CHOP protein expression were observed in the liver. CONCLUSIONS: The novel genetic alteration causing the absence of the EIF2AK3 protein resulted in insufficient handling of severe endoplasmic reticulum stress, leading to liver failure and demise of the patients.


Assuntos
Diabetes Mellitus Tipo 1/genética , Epífises/anormalidades , Mutação INDEL , Osteocondrodisplasias/genética , Sítios de Splice de RNA/genética , eIF-2 Quinase/genética , Pré-Escolar , Consanguinidade , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/patologia , Estresse do Retículo Endoplasmático/genética , Epífises/patologia , Evolução Fatal , Feminino , Mutação da Fase de Leitura , Humanos , Hungria , Lactente , Falência Hepática/complicações , Falência Hepática/genética , Falência Hepática/patologia , Osteocondrodisplasias/diagnóstico , Osteocondrodisplasias/patologia , Linhagem , Irmãos , Viroses/complicações , Viroses/patologia
17.
Physiol Rev ; 100(3): 1349-1414, 2020 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-32031468

RESUMO

The male genital tract (MGT) is the target of a number of viral infections that can have deleterious consequences at the individual, offspring, and population levels. These consequences include infertility, cancers of male organs, transmission to the embryo/fetal development abnormalities, and sexual dissemination of major viral pathogens such as human immunodeficiency virus (HIV) and hepatitis B virus. Lately, two emerging viruses, Zika and Ebola, have additionally revealed that the human MGT can constitute a reservoir for viruses cleared from peripheral circulation by the immune system, leading to their sexual transmission by cured men. This represents a concern for future epidemics and further underlines the need for a better understanding of the interplay between viruses and the MGT. We review here how viruses, from ancient viruses that integrated the germline during evolution through old viruses (e.g., papillomaviruses originating from Neanderthals) and more modern sexually transmitted infections (e.g., simian zoonotic HIV) to emerging viruses (e.g., Ebola and Zika) take advantage of genital tract colonization for horizontal dissemination, viral persistence, vertical transmission, and endogenization. The MGT immune responses to viruses and the impact of these infections are discussed. We summarize the latest data regarding the sources of viruses in semen and the complex role of this body fluid in sexual transmission. Finally, we introduce key animal findings that are relevant for our understanding of viral infection and persistence in the human MGT and suggest future research directions.


Assuntos
Doenças Transmissíveis Emergentes/virologia , Genitália Masculina/virologia , Viroses/virologia , Humanos , Masculino , Viroses/patologia
18.
Lancet Infect Dis ; 20(2): e27-e37, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-32006517

RESUMO

Fever is one of the most common reasons for seeking health care globally and most human pathogens are zoonotic. We conducted a systematic review to describe the occurrence and distribution of zoonotic causes of human febrile illness reported in malaria endemic countries. We included data from 53 (48·2%) of 110 malaria endemic countries and 244 articles that described diagnosis of 30 zoonoses in febrile people. The majority (17) of zoonoses were bacterial, with nine viruses, three protozoa, and one helminth also identified. Leptospira species and non-typhoidal salmonella serovars were the most frequently reported pathogens. Despite evidence of profound data gaps, this Review reveals widespread distribution of multiple zoonoses that cause febrile illness. Greater understanding of the epidemiology of zoonoses in different settings is needed to improve awareness about these pathogens and the management of febrile illness.


Assuntos
Doenças Endêmicas , Febre/epidemiologia , Febre/etiologia , Zoonoses/epidemiologia , Zoonoses/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Infecções Bacterianas/epidemiologia , Infecções Bacterianas/patologia , Criança , Pré-Escolar , Feminino , Helmintíase/epidemiologia , Helmintíase/patologia , Humanos , Lactente , Recém-Nascido , Masculino , Pessoa de Meia-Idade , Infecções por Protozoários/epidemiologia , Infecções por Protozoários/patologia , Viroses/epidemiologia , Viroses/patologia , Adulto Jovem
19.
Int Immunopharmacol ; 80: 106135, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31951958

RESUMO

Inflammation elicited by viral mimetic poly I:C has been shown to impose changes in the expression of drug transporters in the placenta and maternal liver in rats at term pregnancy. This was associated with altered drug disposition in the mother and fetus. Renal transporters play an important role in the elimination of several drugs taken by pregnant women. We examined the impact of poly I:C on the expression of renal transporters in pregnant rats at term. Pregnant Sprague-Dawley rats received single intraperitoneal dose of either poly I:C (5 mg/kg) or saline at gestation day 18 (n = 8/group). Animals were euthanized 24 h after the injection. The mRNA and protein expression of pro-inflammatory cytokines and transporters were measured by qRT-PCR and western blot. Poly I:C caused a fourfold increase in the mRNA of IL-6 in the kidney. As compared to saline controls, the mRNA expression of Mrp2, Bcrp, Octn1, Oat1, Oat2, Oat3, Urat1, Oatp4c1, and Pept2 was downregulated, whereas the Ent1 mRNA was increased. Protein expression of Bcrp, Urat1 and Pept2 were significantly decreased. While there was a trend towards reduced Mrp2, Oat2 and Oat3 protein expression, this did not reach significance. Poly I:C did not impact mRNA levels of Mdr1a, Mdr1b, Mrp4, Oct1, Oct2, Oct3, Octn2, Mate1, Ent2 or Pept1. Viral-induced inflammation mediates significant changes in the expression of several key drug transporters in the kidney of pregnant rats. Many clinically important drugs are substrates for these transporters. Therefore, inflammation-mediated alterations in transporter expression could affect their maternal and fetal disposition.


Assuntos
Regulação da Expressão Gênica/imunologia , Rim/patologia , Proteínas de Membrana Transportadoras/metabolismo , Complicações Infecciosas na Gravidez/imunologia , Viroses/imunologia , Animais , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Feto/imunologia , Feto/patologia , Humanos , Mediadores da Inflamação/metabolismo , Rim/imunologia , Poli I-C/administração & dosagem , Poli I-C/imunologia , Gravidez , Complicações Infecciosas na Gravidez/patologia , Ratos , Viroses/patologia
20.
Dis Markers ; 2020: 9385472, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31998421

RESUMO

Objective: To investigate plasma cytokines (interferon gamma, interleukin-4, and interleukin-17) in patients with viral myocarditis (VMC) and evaluate their predictive value in the progression from VMC to dilated cardiomyopathy (DCM). Methods: A prospective, multicenter, observational study included 536 patients with newly diagnosed VMC admitted in cardiology departments of 24 tertiary super specialised university-affiliated hospitals in the China registry from January 2012 to June 2016. Demographics and clinical characteristics at baseline and after three months were collected, including laboratory blood tests, ECG, echocardiography, and drug treatment in each participating site. The plasma anti-viral antibodies (Abs), anti-heart autoimmune Abs, and cytokines were detected by ELISA. Results: Of the 536 patients, 534 were included for analysis after two patients died in less than a month. The plasma levels of IFN-γ, IL-4, and IL-17 were continually higher in patients with incident DCM than in those without incident DCM at baseline, from the 1st month and the 3rd month; all had a P value of <0.0001. There was a positive correlation between IL-4 and LVEDd (r = 0.30, P < 0.0001) and between IL-17 and LVEDd (r = 0.11, P = 0.02). When all these covariates have entered the model simultaneously, elevated IL-4 and IL-17 were still significantly associated with DCM incidence. The RR (95% CI) of DCM incidence were 1.04 (1.02-1.06) for IL-4 and 5.24 (2.81-9.79) for IL-17. Conclusion: The continued elevation of plasma IL-4 and IL-17 in VMC patients were associated with a high incidence of DCM at three months, and these two cytokines were independent predictors for the progression from VMC to DCM.


Assuntos
Cardiomiopatia Dilatada/sangue , Interleucina-17/sangue , Interleucina-4/sangue , Miocardite/sangue , Viroses/sangue , Adulto , Biomarcadores/sangue , Cardiomiopatia Dilatada/patologia , Feminino , Humanos , Interferon gama/sangue , Masculino , Pessoa de Meia-Idade , Miocardite/patologia , Miocardite/virologia , Viroses/patologia
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