Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 303
Filtrar
1.
IEEE Pulse ; 12(2): 17-21, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33861695

RESUMO

"I am now eight-and-a-half months into my journey with long COVID … My symptoms include diagnosed post-COVID tachycardia and acute fatigue. I also have chest tightness and breathlessness from time to time; anxiety; muscle aches and pains, especially in the evening; memory loss; and insomnia."-38-year-old female from the U.K.


Assuntos
/complicações , Pandemias , Adulto , Autoimunidade , /etiologia , /reabilitação , Disfunção Cognitiva/etiologia , Estudos de Coortes , Fadiga/etiologia , Feminino , Interações entre Hospedeiro e Microrganismos/imunologia , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Masculino , Cidade de Nova Iorque/epidemiologia , Disautonomias Primárias/etiologia , Fatores de Tempo
2.
Int J Mol Med ; 47(4)2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33649798

RESUMO

Severe acute respiratory syndrome (SARS) coronavirus­2 (SARS­CoV­2), the causative viral agent for the ongoing COVID­19 pandemic, enters its host cells primarily via the binding of the SARS­CoV­2 spike (S) proteins to the angiotensin­converting enzyme 2 (ACE2). A number of other cell entry mediators have also been identified, including neuropilin­1 (NRP1) and transmembrane protease serine 2 (TMPRSS2). More recently, it has been demonstrated that transmembrane protease serine 4 (TMPRSS4) along with TMPRSS2 activate the SARS­CoV­2 S proteins, and enhance the viral infection of human small intestinal enterocytes. To date, a systematic analysis of TMPRSS4 in health and disease is lacking. In the present study, using in silico tools, the gene expression and genetic alteration of TMPRSS4 were analysed across numerous tumours and compared to controls. The observations were also expanded to the level of the central nervous system (CNS). The findings revealed that TMPRSS4 was overexpressed in 11 types of cancer, including lung adenocarcinoma, lung squamous cell carcinoma, cervical squamous cell carcinoma, thyroid carcinoma, ovarian cancer, cancer of the rectum, pancreatic cancer, colon and stomach adenocarcinoma, uterine carcinosarcoma and uterine corpus endometrial carcinoma, whilst it was significantly downregulated in kidney carcinomas, acute myeloid leukaemia, skin cutaneous melanoma and testicular germ cell tumours. Finally, a high TMPRSS4 expression was documented in the olfactory tubercle, paraolfactory gyrus and frontal operculum, all brain regions which are associated with the sense of smell and taste. Collectively, these data suggest that TMPRSS4 may play a role in COVID­19 symptomatology as another SARS­CoV­2 host cell entry mediator responsible for the tropism of this coronavirus both in the periphery and the CNS.


Assuntos
/enzimologia , Proteínas de Membrana/genética , /patogenicidade , Serina Endopeptidases/genética , Internalização do Vírus , Encéfalo/enzimologia , Sistema Nervoso Central/enzimologia , Simulação por Computador , Bases de Dados Genéticas , Feminino , Trato Gastrointestinal/enzimologia , Perfilação da Expressão Gênica , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Masculino , Proteínas de Membrana/fisiologia , Neoplasias/enzimologia , Neoplasias/genética , Pandemias , Serina Endopeptidases/fisiologia
3.
J Proteome Res ; 20(3): 1591-1601, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33555895

RESUMO

A novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease 2019 (COVID-19) and continues to be a global health challenge. To understand viral disease biology, we have carried out proteo-genomic analysis using next-generation sequencing (NGS) and mass spectrometry on nasopharyngeal swabs of COVID-19 patients to examine the clinical genome and proteome. Our study confirms the mutability of SARS-CoV-2 showing multiple single-nucleotide polymorphisms. NGS analysis detected 27 mutations, of which 14 are synonymous, 11 are missense, and 2 are extragenic in nature. Phylogenetic analysis of SARS-CoV-2 isolates indicated their close relation to a Bangladesh isolate and multiple origins of isolates within the country. Our proteomic analysis, for the first time, identified 13 different SARS-CoV-2 proteins from the clinical swabs. Of the total 41 peptides captured by high-resolution mass spectrometry, 8 matched to nucleocapsid protein, 2 to ORF9b, and 1 to spike glycoprotein and ORF3a, with remaining peptides mapping to ORF1ab polyprotein. Additionally, host proteome analysis revealed several key host proteins to be uniquely expressed in COVID-19 patients. Pathway analysis of these proteins points toward modulation in immune response, especially involving neutrophil and IL-12-mediated signaling. Besides revealing the aspects of host-virus pathogenesis, our study opens new avenues to develop better diagnostic markers and therapeutic approaches.


Assuntos
/virologia , Polimorfismo de Nucleotídeo Único , /genética , /genética , Genoma Viral , Genômica , Sequenciamento de Nucleotídeos em Larga Escala , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Mutação , Pandemias , Fosfoproteínas/genética , Filogenia , Poliproteínas/genética , Proteoma , Proteômica , /fisiologia , Glicoproteína da Espícula de Coronavírus/genética , Proteínas Virais/genética , /genética
4.
J Proteome Res ; 20(3): 1464-1475, 2021 03 05.
Artigo em Inglês | MEDLINE | ID: mdl-33605735

RESUMO

The SARS-CoV-2 virus is the causative agent of the 2020 pandemic leading to the COVID-19 respiratory disease. With many scientific and humanitarian efforts ongoing to develop diagnostic tests, vaccines, and treatments for COVID-19, and to prevent the spread of SARS-CoV-2, mass spectrometry research, including proteomics, is playing a role in determining the biology of this viral infection. Proteomics studies are starting to lead to an understanding of the roles of viral and host proteins during SARS-CoV-2 infection, their protein-protein interactions, and post-translational modifications. This is beginning to provide insights into potential therapeutic targets or diagnostic strategies that can be used to reduce the long-term burden of the pandemic. However, the extraordinary situation caused by the global pandemic is also highlighting the need to improve mass spectrometry data and workflow sharing. We therefore describe freely available data and computational resources that can facilitate and assist the mass spectrometry-based analysis of SARS-CoV-2. We exemplify this by reanalyzing a virus-host interactome data set to detect protein-protein interactions and identify host proteins that could potentially be used as targets for drug repurposing.


Assuntos
/virologia , Disseminação de Informação/métodos , Espectrometria de Massas/métodos , /química , /tratamento farmacológico , /métodos , Biologia Computacional , Bases de Dados de Proteínas/estatística & dados numéricos , Reposicionamento de Medicamentos , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Espectrometria de Massas/estatística & dados numéricos , Pandemias , Domínios e Motivos de Interação entre Proteínas , Mapas de Interação de Proteínas , Processamento de Proteína Pós-Traducional , Proteômica/métodos , Proteômica/estatística & dados numéricos , /fisiologia , Proteínas Virais/química , Proteínas Virais/fisiologia
5.
Nat Commun ; 12(1): 942, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33574256

RESUMO

The mosquito microbiota impacts the physiology of its host and is essential for normal larval development, thereby influencing transmission of vector-borne pathogens. Germ-free mosquitoes generated with current methods show larval stunting and developmental deficits. Therefore, functional studies of the mosquito microbiota have so far mostly been limited to antibiotic treatments of emerging adults. In this study, we introduce a method to produce germ-free Aedes aegypti mosquitoes. It is based on reversible colonisation with bacteria genetically modified to allow complete decolonisation at any developmental stage. We show that, unlike germ-free mosquitoes previously produced using sterile diets, reversibly colonised mosquitoes show no developmental retardation and reach the same size as control adults. This allows us to uncouple the study of the microbiota in larvae and adults. In adults, we detect no impact of bacterial colonisation on mosquito fecundity or longevity. In larvae, data from our transcriptome analysis and diet supplementation experiments following decolonisation suggest that bacteria support larval development by contributing to folate biosynthesis and by enhancing energy storage. Our study establishes a tool to study the microbiota in insects and deepens our knowledge on the metabolic contribution of bacteria to mosquito development.


Assuntos
Interações entre Hospedeiro e Microrganismos/fisiologia , Microbiota/fisiologia , Mosquitos Vetores/microbiologia , Aedes/genética , Aedes/crescimento & desenvolvimento , Aedes/microbiologia , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/crescimento & desenvolvimento , Ácido Fólico , Alimentos Fortificados , Trato Gastrointestinal/microbiologia , Regulação da Expressão Gênica , Vida Livre de Germes , Larva/genética , Larva/crescimento & desenvolvimento , Larva/microbiologia , Metabolismo dos Lipídeos , Mosquitos Vetores/crescimento & desenvolvimento , RNA Ribossômico 16S
6.
PLoS Comput Biol ; 17(2): e1008686, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33544720

RESUMO

The novelty of new human coronavirus COVID-19/SARS-CoV-2 and the lack of effective drugs and vaccines gave rise to a wide variety of strategies employed to fight this worldwide pandemic. Many of these strategies rely on the repositioning of existing drugs that could shorten the time and reduce the cost compared to de novo drug discovery. In this study, we presented a new network-based algorithm for drug repositioning, called SAveRUNNER (Searching off-lAbel dRUg aNd NEtwoRk), which predicts drug-disease associations by quantifying the interplay between the drug targets and the disease-specific proteins in the human interactome via a novel network-based similarity measure that prioritizes associations between drugs and diseases locating in the same network neighborhoods. Specifically, we applied SAveRUNNER on a panel of 14 selected diseases with a consolidated knowledge about their disease-causing genes and that have been found to be related to COVID-19 for genetic similarity (i.e., SARS), comorbidity (e.g., cardiovascular diseases), or for their association to drugs tentatively repurposed to treat COVID-19 (e.g., malaria, HIV, rheumatoid arthritis). Focusing specifically on SARS subnetwork, we identified 282 repurposable drugs, including some the most rumored off-label drugs for COVID-19 treatments (e.g., chloroquine, hydroxychloroquine, tocilizumab, heparin), as well as a new combination therapy of 5 drugs (hydroxychloroquine, chloroquine, lopinavir, ritonavir, remdesivir), actually used in clinical practice. Furthermore, to maximize the efficiency of putative downstream validation experiments, we prioritized 24 potential anti-SARS-CoV repurposable drugs based on their network-based similarity values. These top-ranked drugs include ACE-inhibitors, monoclonal antibodies (e.g., anti-IFNγ, anti-TNFα, anti-IL12, anti-IL1ß, anti-IL6), and thrombin inhibitors. Finally, our findings were in-silico validated by performing a gene set enrichment analysis, which confirmed that most of the network-predicted repurposable drugs may have a potential treatment effect against human coronavirus infections.


Assuntos
Algoritmos , Antivirais/farmacologia , Reposicionamento de Medicamentos/métodos , Pandemias , /epidemiologia , Ensaios Clínicos como Assunto , Comorbidade , Biologia Computacional , Simulação por Computador , Descoberta de Drogas , Avaliação Pré-Clínica de Medicamentos/métodos , Avaliação Pré-Clínica de Medicamentos/estatística & dados numéricos , Reposicionamento de Medicamentos/estatística & dados numéricos , Interações entre Hospedeiro e Microrganismos/efeitos dos fármacos , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Mapas de Interação de Proteínas/efeitos dos fármacos , /efeitos dos fármacos
7.
Stem Cell Reports ; 16(3): 493-504, 2021 03 09.
Artigo em Inglês | MEDLINE | ID: mdl-33626333

RESUMO

Enteroviruses, such as EV-A71 and CVA16, mainly infect the human gastrointestinal tract. Human coronaviruses, including SARS-CoV and SARS-CoV-2, have been variably associated with gastrointestinal symptoms. We aimed to optimize the human intestinal organoids and hypothesize that these optimized intestinal organoids can recapitulate enteric infections of enterovirus and coronavirus. We demonstrate that the optimized human intestinal organoids enable better simulation of the native human intestinal epithelium, and that they are significantly more susceptible to EV-A71 than CVA16. Higher replication of EV-A71 than CVA16 in the intestinal organoids triggers a more vigorous cellular response. However, SARS-CoV and SARS-CoV-2 exhibit distinct dynamics of virus-host interaction; more robust propagation of SARS-CoV triggers minimal cellular response, whereas, SARS-CoV-2 exhibits lower replication capacity but elicits a moderate cellular response. Taken together, the disparate profile of the virus-host interaction of enteroviruses and coronaviruses in human intestinal organoids may unravel the cellular basis of the distinct pathogenicity of these viral pathogens.


Assuntos
/virologia , Enterovirus Humano A/patogenicidade , Infecções por Enterovirus/virologia , Intestinos/virologia , Organoides/virologia , /patogenicidade , Animais , Linhagem Celular , Chlorocebus aethiops , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Mucosa Intestinal/virologia , Células Vero , Replicação Viral/fisiologia
8.
Exp Biol Med (Maywood) ; 246(7): 749-757, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33467896

RESUMO

Posttranslational modification of proteins, which include both the enzymatic alterations of protein side chains and main-chain peptide bond connectivity, is a fundamental regulatory process that is crucial for almost every aspects of cell biology, including the virus-host cell interaction and the SARS-CoV-2 infection. The posttranslational modification of proteins has primarily been studied in cells and tissues in an intra-proteomic context (where both substrates and enzymes are part of the same species). However, the inter-proteomic posttranslational modifications of most of the SARS-CoV-2 proteins by the host enzymes and vice versa are largely unexplored in virus pathogenesis and in the host immune response. It is now known that the structural spike (S) protein of the SARS-CoV-2 undergoes proteolytic priming by the host serine proteases for entry into the host cells, and N- and O-glycosylation by the host cell enzymes during virion packaging, which enable the virus to spread. New evidence suggests that both SARS-CoV-2 and the host proteins undergo inter-proteomic posttranslational modifications, which play roles in virus pathogenesis and infection-induced immune response by hijacking the host cell signaling. The purpose of this minireview is to bring attention of the scientific community to recent cutting-edge discoveries in this understudied area. It is likely that a better insight into the molecular mechanisms involved may open new research directions, and thereby contribute to novel therapeutic modality development against the SARS-CoV-2. Here we briefly discuss the rationale and touch upon some unanswered questions in this context, especially those that require attention from the scientific community.


Assuntos
/metabolismo , Interações entre Hospedeiro e Microrganismos/fisiologia , Processamento de Proteína Pós-Traducional , Proteínas Virais/metabolismo , Glicosilação , Humanos , Fosforilação , Ubiquitina
9.
Sci Signal ; 14(665)2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436498

RESUMO

The spike protein of SARS-CoV-2 binds the angiotensin-converting enzyme 2 (ACE2) on the host cell surface and subsequently enters host cells through receptor-mediated endocytosis. Additional cell receptors may be directly or indirectly involved, including integrins. The cytoplasmic tails of ACE2 and integrins contain several predicted short linear motifs (SLiMs) that may facilitate internalization of the virus as well as its subsequent propagation through processes such as autophagy. Here, we measured the binding affinity of predicted interactions between SLiMs in the cytoplasmic tails of ACE2 and integrin ß3 with proteins that mediate endocytic trafficking and autophagy. We validated that a class I PDZ-binding motif mediated binding of ACE2 to the scaffolding proteins SNX27, NHERF3, and SHANK, and that a binding site for the clathrin adaptor AP2 µ2 in ACE2 overlaps with a phospho-dependent binding site for the SH2 domains of Src family tyrosine kinases. Furthermore, we validated that an LC3-interacting region (LIR) in integrin ß3 bound to the ATG8 domains of the autophagy receptors MAP1LC3 and GABARAP in a manner enhanced by LIR-adjacent phosphorylation. Our results provide molecular links between cell receptors and mediators of endocytosis and autophagy that may facilitate viral entry and propagation.


Assuntos
/fisiologia , Integrina beta3/fisiologia , Receptores Virais/fisiologia , /patogenicidade , Internalização do Vírus , Sequência de Aminoácidos , /genética , Autofagia/fisiologia , Endocitose/fisiologia , Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Integrina beta3/química , Integrina beta3/genética , Modelos Moleculares , Pandemias , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/genética , Fragmentos de Peptídeos/fisiologia , Fosforilação , Ligação Proteica , Domínios e Motivos de Interação entre Proteínas , Sinais Direcionadores de Proteínas/genética , Sinais Direcionadores de Proteínas/fisiologia , Receptores Virais/química , Receptores Virais/genética , /genética
10.
Sci Signal ; 14(665)2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33436497

RESUMO

The first reported receptor for SARS-CoV-2 on host cells was the angiotensin-converting enzyme 2 (ACE2). However, the viral spike protein also has an RGD motif, suggesting that cell surface integrins may be co-receptors. We examined the sequences of ACE2 and integrins with the Eukaryotic Linear Motif (ELM) resource and identified candidate short linear motifs (SLiMs) in their short, unstructured, cytosolic tails with potential roles in endocytosis, membrane dynamics, autophagy, cytoskeleton, and cell signaling. These SLiM candidates are highly conserved in vertebrates and may interact with the µ2 subunit of the endocytosis-associated AP2 adaptor complex, as well as with various protein domains (namely, I-BAR, LC3, PDZ, PTB, and SH2) found in human signaling and regulatory proteins. Several motifs overlap in the tail sequences, suggesting that they may act as molecular switches, such as in response to tyrosine phosphorylation status. Candidate LC3-interacting region (LIR) motifs are present in the tails of integrin ß3 and ACE2, suggesting that these proteins could directly recruit autophagy components. Our findings identify several molecular links and testable hypotheses that could uncover mechanisms of SARS-CoV-2 attachment, entry, and replication against which it may be possible to develop host-directed therapies that dampen viral infection and disease progression. Several of these SLiMs have now been validated to mediate the predicted peptide interactions.


Assuntos
/virologia , Interações entre Hospedeiro e Microrganismos/fisiologia , /patogenicidade , Internalização do Vírus , Sequência de Aminoácidos , /genética , Animais , Sequência Conservada , Interações entre Hospedeiro e Microrganismos/genética , Humanos , Integrinas/química , Integrinas/genética , Integrinas/fisiologia , Proteínas Intrinsicamente Desordenadas/química , Proteínas Intrinsicamente Desordenadas/genética , Proteínas Intrinsicamente Desordenadas/fisiologia , Modelos Biológicos , Modelos Moleculares , Oligopeptídeos/química , Oligopeptídeos/genética , Oligopeptídeos/fisiologia , Domínios e Motivos de Interação entre Proteínas/genética , Domínios e Motivos de Interação entre Proteínas/fisiologia , Sinais Direcionadores de Proteínas/genética , Sinais Direcionadores de Proteínas/fisiologia , Receptores Virais/química , Receptores Virais/genética , Receptores Virais/fisiologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/fisiologia
11.
Sci Rep ; 11(1): 2459, 2021 01 28.
Artigo em Inglês | MEDLINE | ID: mdl-33510359

RESUMO

A deeper understanding of the molecular biology of SARS-CoV-2 infection, including the host response to the virus, is urgently needed. Commonalities exist between the host immune response to viral infections and cancer. Here, we defined transcriptional signatures of SARS-CoV-2 infection involving hundreds of genes common across lung adenocarcinoma cell lines (A549, Calu-3) and normal human bronchial epithelial cells (NHBE), with additional signatures being specific to one or both adenocarcinoma lines. Cross-examining eight transcriptomic databases, we found that host transcriptional responses of lung adenocarcinoma cells to SARS-CoV-2 infection shared broad similarities with host responses to multiple viruses across different model systems and patient samples. Furthermore, these SARS-CoV-2 transcriptional signatures were manifested within specific subsets of human cancer, involving ~ 20% of cases across a wide range of histopathological types. These cancer subsets show immune cell infiltration and inflammation and involve pathways linked to the SARS-CoV-2 response, such as immune checkpoint, IL-6, type II interferon signaling, and NF-κB. The cell line data represented immune responses activated specifically within the cancer cells of the tumor. Common genes and pathways implicated as part of the viral host response point to therapeutic strategies that may apply to both SARS-CoV-2 and cancer.


Assuntos
/genética , Interações entre Hospedeiro e Microrganismos/fisiologia , /fisiologia , Células A549 , Brônquios/metabolismo , Células Epiteliais/metabolismo , Células Epiteliais/virologia , Humanos , Imunidade , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/virologia , /metabolismo , Transcrição Genética , Transcriptoma , Replicação Viral/genética
12.
Am J Physiol Lung Cell Mol Physiol ; 320(2): L257-L265, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33355522

RESUMO

The novel SARS-CoV-2 coronavirus, which is responsible for COVID-19 disease, was first reported in Wuhan, China, in December of 2019. The virus rapidly spread, and the World Health Organization declared a pandemic by March 2020. With millions of confirmed cases worldwide, there is growing concern and considerable debate regarding the potential for coronavirus infection to contribute to an appreciable burden of chronic respiratory symptoms or fibrotic disease among recovered individuals. Because the first case of COVID-19 was documented less than one year ago, data regarding long-term clinical outcomes are not yet available, and predictions for long-term outcome are speculative at best. However, due to the staggering number of cases and the severity of disease in many individuals, there is a critical need to consider the potential long-term implications of COVID-19. This review examines current basic and clinical data regarding fibrogenic mechanisms of viral injury in the context of SARS-CoV-2. Several intersecting mechanisms between coronavirus infection and fibrotic pathways are discussed to highlight factors and processes that may be targetable to improve patient outcome. Reports of post-infection sequelae from previous coronavirus outbreaks are presented toward the goal of improved recognition of potential contributing risk factors for fibrotic disease.


Assuntos
/complicações , Pandemias , Fibrose Pulmonar/etiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , /virologia , Citocinas/fisiologia , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Inflamação/etiologia , Inflamação/virologia , Fibrose Pulmonar/virologia , Respiração Artificial/efeitos adversos , /etiologia , Fatores de Risco , /fisiologia , Transdução de Sinais , Sobreviventes
14.
Sci Rep ; 10(1): 22424, 2020 12 30.
Artigo em Inglês | MEDLINE | ID: mdl-33380734

RESUMO

Root-associated entomopathogenic fungi (R-AEF) indirectly influence herbivorous insect performance. However, host plant-R-AEF interactions and R-AEF as biological control agents have been studied independently and without much attention to the potential synergy between these functional traits. In this study, we evaluated behavioral responses of cabbage root flies [Delia radicum L. (Diptera: Anthomyiidae)] to a host plant (white cabbage cabbage Brassica oleracea var. capitata f. alba cv. Castello L.) with and without the R-AEF Metarhizium brunneum (Petch). We performed experiments on leaf reflectance, phytohormonal composition and host plant location behavior (behavioral processes that contribute to locating and selecting an adequate host plant in the environment). Compared to control host plants, R-AEF inoculation caused, on one hand, a decrease in reflectance of host plant leaves in the near-infrared portion of the radiometric spectrum and, on the other, an increase in the production of jasmonic, (+)-7-iso-jasmonoyl-L-isoleucine and salicylic acid in certain parts of the host plant. Under both greenhouse and field settings, landing and oviposition by cabbage root fly females were positively affected by R-AEF inoculation of host plants. The fungal-induced change in leaf reflectance may have altered visual cues used by the cabbage root flies in their host plant selection. This is the first study providing evidence for the hypothesis that R-AEF manipulate the suitability of their host plant to attract herbivorous insects.


Assuntos
Brassica/microbiologia , Brassica/parasitologia , Dípteros/fisiologia , Herbivoria/fisiologia , Metarhizium/patogenicidade , Animais , Brassica/metabolismo , Feminino , Interações entre Hospedeiro e Microrganismos/fisiologia , Modelos Biológicos , Oviposição , Controle Biológico de Vetores , Folhas de Planta/metabolismo , Raízes de Plantas/microbiologia , Simbiose
16.
Nat Commun ; 11(1): 5206, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060586

RESUMO

Variation in the human gut microbiome can reflect host lifestyle and behaviors and influence disease biomarker levels in the blood. Understanding the relationships between gut microbes and host phenotypes are critical for understanding wellness and disease. Here, we examine associations between the gut microbiota and ~150 host phenotypic features across ~3,400 individuals. We identify major axes of taxonomic variance in the gut and a putative diversity maximum along the Firmicutes-to-Bacteroidetes axis. Our analyses reveal both known and unknown associations between microbiome composition and host clinical markers and lifestyle factors, including host-microbe associations that are composition-specific. These results suggest potential opportunities for targeted interventions that alter the composition of the microbiome to improve host health. By uncovering the interrelationships between host diet and lifestyle factors, clinical blood markers, and the human gut microbiome at the population-scale, our results serve as a roadmap for future studies on host-microbe interactions and interventions.


Assuntos
Biomarcadores , Doença , Microbioma Gastrointestinal/fisiologia , Saúde , Interações entre Hospedeiro e Microrganismos/fisiologia , Adulto , Biodiversidade , Dieta , Feminino , Firmicutes , Microbioma Gastrointestinal/genética , Humanos , Estilo de Vida , Masculino , Pessoa de Meia-Idade , RNA Ribossômico 16S/genética , Biologia de Sistemas
17.
Nat Commun ; 11(1): 5189, 2020 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-33060596

RESUMO

Among the various host cellular processes that are hijacked by flaviviruses, few mechanisms have been described with regard to viral egress. Here we investigate how flaviviruses exploit Src family kinases (SFKs) for exit from infected cells. We identify Lyn as a critical component for secretion of Dengue and Zika infectious particles and their corresponding virus like particles (VLPs). Pharmacological inhibition or genetic depletion of the SFKs, Lyn in particular, block virus secretion. Lyn-/- cells are impaired in virus release and are rescued when reconstituted with wild-type Lyn, but not a kinase- or palmitoylation-deficient Lyn mutant. We establish that virus particles are secreted in two distinct populations - one as free virions and the other enclosed within membranes. Lyn is critical for the latter, which consists of proteolytically processed, infectious virus progenies within autophagosome-derived vesicles. This process depends on Ulk1, Rab GTPases and SNARE complexes implicated in secretory but not degradative autophagy and occur with significantly faster kinetics than the conventional secretory pathway. Our study reveals a previously undiscovered Lyn-dependent exit route of flaviviruses in LC3+ secretory organelles that enables them to evade circulating antibodies and might affect tissue tropism.


Assuntos
Autofagossomos/metabolismo , Autofagossomos/virologia , Flavivirus/metabolismo , Quinases da Família src/metabolismo , Animais , Autofagia , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Linhagem Celular , Chlorocebus aethiops , Dengue , Vírus da Dengue/metabolismo , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas SNARE/metabolismo , Via Secretória , Células Vero , Vírion/metabolismo , Liberação de Vírus , Zika virus/metabolismo , Infecção por Zika virus , Proteínas rab de Ligação ao GTP/metabolismo , Quinases da Família src/genética
18.
Electromagn Biol Med ; 39(4): 433-436, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33016156

RESUMO

To help investigate the relationship between inflammatory and other symptoms of coronavirus and the protein-protein interactions (PPI) that occur between viral proteins and protein molecules of the host cell, I propose that the electrostatic discharge (ESD) exists including corona discharge to lead to ozone gas. I cite evidence in support of this hypothesis. I hope that the proposed will inspire new studies in finding effective treatments and vaccines for individuals with coronavirus disease in 2019. I suggest possible future studies that may lend more credibility to the proposed.


Assuntos
Betacoronavirus/fisiologia , Coronavirus/fisiologia , Modelos Biológicos , Eletricidade Estática , Betacoronavirus/química , Betacoronavirus/patogenicidade , Coronavirus/patogenicidade , Infecções por Coronavirus/tratamento farmacológico , Infecções por Coronavirus/fisiopatologia , Infecções por Coronavirus/virologia , Sistema de Condução Cardíaco/efeitos dos fármacos , Sistema de Condução Cardíaco/fisiopatologia , Interações entre Hospedeiro e Microrganismos/fisiologia , Humanos , Hidroxicloroquina/farmacologia , Ozônio/metabolismo , Ozônio/toxicidade , Perda de Ozônio , Pandemias , Pneumonia Viral/tratamento farmacológico , Pneumonia Viral/fisiopatologia , Pneumonia Viral/virologia , Domínios e Motivos de Interação entre Proteínas/fisiologia , Glicoproteína da Espícula de Coronavírus/química , Glicoproteína da Espícula de Coronavírus/fisiologia
19.
Sheng Wu Gong Cheng Xue Bao ; 36(8): 1471-1483, 2020 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-32924346

RESUMO

Autophagy is a highly conserved degradation process that targets cytoplasmic components, maintains metabolic stability in cells, and combates infection with various pathogenic bacteria. Autophagy can help body to eliminate invading pathogens; however, some bacteria have evolved multiple strategies to interfere with the autophagy signaling pathway or inhibit the fusion of autophagosomes with lysosomes to form autolysosomes to escape autophagic degradation, and even use autophagy to promote their growth and proliferation. This review discusses the newest progress in the relationship between pathogens and autophagy of host cell, and the role of autophagy in bacterial infection. We hope that this review provides useful knowledge for the research on autophagy caused by pathogenic infection.


Assuntos
Autofagia , Fenômenos Fisiológicos Bacterianos , Interações entre Hospedeiro e Microrganismos , Autofagia/fisiologia , Bactérias/metabolismo , Citoplasma , Interações entre Hospedeiro e Microrganismos/fisiologia , Transdução de Sinais
20.
PLoS One ; 15(8): e0234099, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32810132

RESUMO

Two common ecological assumptions are that host generalist and rare species are poorer competitors relative to host specialist and more abundant counterparts. While these assumptions have received considerable study in both plant and animals, how they apply to ectomycorrhizal fungi remains largely unknown. To investigate how interspecific competition may influence the anomalous host associations of the rare ectomycorrhizal generalist fungus, Suillus subaureus, we conducted a seedling bioassay. Pinus strobus seedlings were inoculated in single- or two-species treatments of three Suillus species: S. subaureus, S. americanus, and S. spraguei. After 4 and 8 months of growth, seedlings were harvested and scored for mycorrhizal colonization as well as dry biomass. At both time points, we found a clear competitive hierarchy among the three ectomycorrhizal fungal species: S. americanus > S. subaureus > S. spraguei, with the competitive inferior, S. spraguei, having significantly delayed colonization relative to S. americanus and S. subaureus. In the single-species treatments, we found no significant differences in the dry biomasses of P. strobus seedlings colonized by each Suillus species, suggesting none was a more effective plant symbiont. Taken together, these results indicate that the rarity and anomalous host associations exhibited by S. subaureus in natural settings are not driven by inherently poor competitive ability or host growth promotion, but that the timing of colonization is a key factor determining the outcome of ectomycorrhizal fungal competitive interactions.


Assuntos
Micorrizas/crescimento & desenvolvimento , Pinus/microbiologia , Simbiose/fisiologia , Basidiomycota/classificação , Basidiomycota/genética , Basidiomycota/crescimento & desenvolvimento , Biomassa , Interações entre Hospedeiro e Microrganismos/fisiologia , Especificidade de Hospedeiro/genética , Especificidade de Hospedeiro/fisiologia , Pinus/crescimento & desenvolvimento , Raízes de Plantas/microbiologia , Plântula/crescimento & desenvolvimento , Plântula/microbiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...