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1.
J Microbiol ; 57(9): 803-811, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31452044

RESUMO

Middle East respiratory syndrome coronavirus (MERS-CoV) is a causative agent of severe-to-fatal pneumonia especially in patients with pre-existing conditions, such as smoking and chronic obstructive pulmonary disease (COPD). MERS-CoV transmission continues to be reported in the Saudi Arabian Peninsula since its discovery in 2012. However, it has rarely been epidemic outside the area except one large outbreak in South Korea in May 2015. The genome of the epidemic MERS-CoV isolated from a Korean patient revealed its homology to previously reported strains. MERS-CoV encodes 5 accessory proteins and generally, they do not participate in the genome transcription and replication but rather are involved in viral evasion of the host innate immune responses. Here we report that ORF8b, an accessory protein of MERS-CoV, strongly inhibits both MDA5- and RIG-I-mediated activation of interferon beta promoter activity while downstream signaling molecules were left largely unaffected. Of note, MDA5 protein levels were significantly down-regulated by ORF8b and co-expression of ORF4a and ORF4b. These novel findings will facilitate elucidation of mechanisms of virus-encoded evasion strategies, thus helping design rationale antiviral countermeasures against deadly MERS-CoV infection.


Assuntos
Infecções por Coronavirus/genética , Interferon beta/genética , Coronavírus da Síndrome Respiratória do Oriente Médio/metabolismo , Regiões Promotoras Genéticas , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Proteína DEAD-box 58/genética , Proteína DEAD-box 58/metabolismo , Desenho de Drogas , Interações Hospedeiro-Patógeno , Humanos , Helicase IFIH1 Induzida por Interferon/genética , Helicase IFIH1 Induzida por Interferon/metabolismo , Interferon beta/metabolismo , Coronavírus da Síndrome Respiratória do Oriente Médio/genética , Arábia Saudita , Vacinas Virais/genética , Vacinas Virais/imunologia
2.
J Agric Food Chem ; 67(31): 8476-8484, 2019 Aug 07.
Artigo em Inglês | MEDLINE | ID: mdl-31298527

RESUMO

Cicada flowers, which are edible and medicinal mushrooms, are the fruiting bodies of Isaria cicadae, a fungus that is parasitic on the larvae of cicada pupae. We hypothesize that host factors might possess stimulatory activity on metabolite synthesis in Isaria cicadae. Here, we first compared the microbial community structures of different wild cicada flowers across geographical regions, compartments, and growth stages via high-throughput sequencing. Isaria cicadae TZC-3, an isolate of the most abundant operational taxonomic unit (OTU6782) in all the fungal communities, was isolated from wild cicada flowers. Furthermore, the effects of cicada pupae on metabolite synthesis in Isaria cicadae TZC-3 were studied in submerged culture. The contents of intercellular polysaccharides, adenosine, N6-(2-hydroxyethyl)-adenosine, free amino acids, and hydrolyzed monosaccharides in the mycelia cultured with cicada pupa powder (4%) were significantly increased as compared with the contents in the control group. This indicates that a cicada pupa can act as an elicitor for metabolite synthesis in Isaria cicadae.


Assuntos
Cordyceps/metabolismo , Carpóforos/química , Hemípteros/microbiologia , Pupa/microbiologia , Adenosina/análise , Adenosina/metabolismo , Aminoácidos/análise , Aminoácidos/metabolismo , Animais , Cordyceps/química , Cordyceps/crescimento & desenvolvimento , Carpóforos/crescimento & desenvolvimento , Carpóforos/metabolismo , Hemípteros/química , Hemípteros/metabolismo , Interações Hospedeiro-Patógeno , Microbiota , Micélio/química , Micélio/crescimento & desenvolvimento , Micélio/metabolismo , Pupa/química , Pupa/metabolismo
3.
Microbiol Res ; 226: 27-33, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31284941

RESUMO

Postbloom fruit drop (PFD), caused mainly by Colletotrichum abscissum, is one of the most severe citrus diseases and can causes up to 80% fruit loss in favorable climatic conditions. According to the literature, other Colletotrichum species colonize hosts using distinct strategies: intracellular hemibiotrophic or subcuticular intramural necrotrophic colonization. However, so far, for C. abscissum only the necrotrophic stage has been described and some aspects remain unclear in PFD disease cycle. To better understand the disease cycle, microscopy studies could be applied. However, even using eGFP strains (expressing green fluorescent protein), the results are unclear due to the autofluorescence of citrus leaves. To eliminate this problem and to study the interaction between C. abscissum-citrus we used a destaining and staining methodologies, and we observed that in leaves, even applying injury before inoculation, C. abscissum does not colonize adjacent tissues. Apparently, in the leaves the fungus only uses the nutrients exposed in the artificial lesions for growth, and then produces large amount of spores. However, in flowers, C. abscissum penetrated and colonized the tissues of the petals 12 h after inoculation. In the early stages of infection, we observed the development of primary biotrophic hyphae, suggesting this species as a hemibiotrophic fungus, with a short biotrophic phase during flower colonization followed by dominant necrotrophic colonization. In conclusion, the use of an eGFP strain of C. abscissum and a different methodology of destaining and staining allowed a better understanding of the morphology and mechanisms used by this citrus pathogen to colonize the host.


Assuntos
Citrus/microbiologia , Colletotrichum/citologia , Colletotrichum/crescimento & desenvolvimento , Colletotrichum/patogenicidade , Doenças das Plantas/microbiologia , Flores/microbiologia , Frutas/microbiologia , Proteínas de Fluorescência Verde , Interações Hospedeiro-Patógeno , Hifas/citologia , Hifas/crescimento & desenvolvimento , Microscopia/métodos , Microscopia Confocal/métodos , Folhas de Planta , Esporos Fúngicos/citologia
4.
Arch Insect Biochem Physiol ; 102(1): e21598, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31290186

RESUMO

At present, the effect of ultraviolet (UV) radiation on the interaction between Bombyx mori nucleopolyhedrovirus (BmNPV) and host remains unclear. In the current study, UV treatment significantly reduced the activity of BmNPV budded viruses (BVs), and UV-damaged BmN cells were not conducive to BmNPV proliferation. BmNPV infection significantly reduced the viability of host cells, but increased the viability of high-dose UV-treated host cells. Furthermore, the quantitative reverse-transcription PCR (qPCR) results suggested that BmNPV and Bombyx mori might mutually use the same DNA repair proteins for repairing UV-induced damage and BmNPV infection promote the ability of host cells to repair UV-induced damage.


Assuntos
Bombyx/virologia , Interações Hospedeiro-Patógeno/efeitos da radiação , Nucleopolyhedrovirus/efeitos da radiação , Animais , Bombyx/imunologia , Bombyx/metabolismo , Bombyx/efeitos da radiação , Sobrevivência Celular , Células Cultivadas , Endonucleases Flap/metabolismo , Neuropeptídeos/metabolismo , Raios Ultravioleta
5.
J Agric Food Chem ; 67(33): 9265-9276, 2019 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-31361479

RESUMO

Fungal infections significantly alter the emissions of volatile organic compounds (VOCs) by plants, but the mechanisms for VOCs affecting fungal infections of plants remain largely unknown. Here, we found that infection by Botrytis cinerea upregulated linalool production by strawberries and fumigation with linalool was able to inhibit the infection of fruits by the fungus. Linalool treatment downregulated the expression of rate-limiting enzymes in the ergosterol biosynthesis pathway, and this reduced the ergosterol content in the fungi cell membrane and impaired membrane integrity. Linalool treatment also caused damage to mitochondrial membranes by collapsing mitochondrial membrane potential and also downregulated genes involved in adenosine triphosphate (ATP) production, resulting in a significant decrease in the ATP content. Linalool treatment increased the levels of reactive oxygen species (ROS), in response to which the treated fungal cells produced more of the ROS scavenger pyruvate. RNA-Seq and proteomic analysis data showed that linalool treatment slowed the rates of transcription and translation.


Assuntos
Botrytis/efeitos dos fármacos , Fragaria/metabolismo , Frutas/microbiologia , Monoterpenos/metabolismo , Doenças das Plantas/microbiologia , Compostos Orgânicos Voláteis/metabolismo , Trifosfato de Adenosina/metabolismo , Botrytis/crescimento & desenvolvimento , Fragaria/química , Fragaria/microbiologia , Frutas/química , Frutas/metabolismo , Interações Hospedeiro-Patógeno , Membranas Mitocondriais/efeitos dos fármacos , Membranas Mitocondriais/metabolismo , Monoterpenos/farmacologia , Doenças das Plantas/prevenção & controle , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteômica , Espécies Reativas de Oxigênio/metabolismo , Compostos Orgânicos Voláteis/farmacologia
6.
BMC Plant Biol ; 19(1): 320, 2019 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-31319813

RESUMO

BACKGROUND: Plant cell walls participate in all plant-environment interactions. Maintaining cell wall integrity (CWI) during these interactions is essential. This realization led to increased interest in CWI and resulted in knowledge regarding early perception and signalling mechanisms active during CWI maintenance. By contrast, knowledge regarding processes mediating changes in cell wall metabolism upon CWI impairment is very limited. RESULTS: To identify genes involved and to investigate their contributions to the processes we selected 23 genes with altered expression in response to CWI impairment and characterized the impact of T-DNA insertions in these genes on cell wall composition using Fourier-Transform Infrared Spectroscopy (FTIR) in Arabidopsis thaliana seedlings. Insertions in 14 genes led to cell wall phenotypes detectable by FTIR. A detailed analysis of four genes found that their altered expression upon CWI impairment is dependent on THE1 activity, a key component of CWI maintenance. Phenotypic characterizations of insertion lines suggest that the four genes are required for particular aspects of CWI maintenance, cell wall composition or resistance to Plectosphaerella cucumerina infection in adult plants. CONCLUSION: Taken together, the results implicate the genes in responses to CWI impairment, cell wall metabolism and/or pathogen defence, thus identifying new molecular components and processes relevant for CWI maintenance.


Assuntos
Arabidopsis/genética , Parede Celular/metabolismo , Genes de Plantas/fisiologia , Arabidopsis/metabolismo , Arabidopsis/fisiologia , Ascomicetos , Parede Celular/fisiologia , Resistência à Doença/genética , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas/genética , Técnicas de Silenciamento de Genes , Interações Hospedeiro-Patógeno , Doenças das Plantas/imunologia , Plântula/metabolismo , Plântula/fisiologia , Espectroscopia de Infravermelho com Transformada de Fourier
7.
Vet Microbiol ; 233: 140-146, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31176400

RESUMO

Porcine reproductive and respiratory syndrome (PRRS) is caused by PRRS virus (PRRSV), and is characterized by respiratory diseases in piglet and reproductive disorders in sow. Identification of sustainable and effective measures to mitigate PRRSV transmission is a pressing problem. The nucleocapsid (N) protein of PRRSV plays a crucial role in inhibiting host innate immunity during PRRSV infection. In the current study, a new host-restricted factor, tripartite motif protein 25 (TRIM25), was identified as an inhibitor of PRRSV replication. Co-immunoprecipitation assay indicated that the PRRSV N protein interferes with TRIM25-RIG-I interactions by competitively interacting with TRIM25. Furthermore, N protein inhibits the expression of TRIM25 and TRIM25-mediated RIG-I ubiquitination to suppress interferon ß production. Furthermore, with increasing TRIM25 expression, the inhibitory effect of N protein on the ubiquitination of RIG-I diminished. These results indicate for the first time that TRIM25 inhibits PRRSV replication and that the N protein antagonizes the antiviral activity by interfering with TRIM25-mediated RIG-I ubiquitination. This not only provides a theoretical basis for the development of drugs to control PRRSV replication, but also better explains the mechanism through which the PRRSV N protein inhibits innate immune responses of the host.


Assuntos
Proteína DEAD-box 58/metabolismo , Proteínas do Nucleocapsídeo/metabolismo , Vírus da Síndrome Respiratória e Reprodutiva Suína/metabolismo , Proteínas com Motivo Tripartido/antagonistas & inibidores , Proteínas com Motivo Tripartido/genética , Ubiquitinação , Motivos de Aminoácidos , Animais , Linhagem Celular , Cercopithecus aethiops , Células HEK293 , Interações Hospedeiro-Patógeno , Humanos , Imunidade Inata , Proteínas do Nucleocapsídeo/genética , Vírus da Síndrome Respiratória e Reprodutiva Suína/genética , Ligação Proteica , RNA Interferente Pequeno , Transdução de Sinais/imunologia , Suínos , Transfecção , Replicação Viral
8.
Vet Microbiol ; 233: 164-173, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31176404

RESUMO

Exosomes are small membrane-enclosed vesicles that participate in intercellular communication between cells. Numerous evidences suggested that exosomes derived from virus-infected cells can mediate virus transmission or/and regulate immune response. Foot-and-mouth disease virus (FMDV) is the prototype member of the Aphthovirus genus of the Picornaviridae family. It can cause highly infectious disease of cloven-hoofed livestock and significantly increase public awareness. However, the role of exosomes in the transmission of FMDV has still remained unknown. In this study, full length of FMDV genomic RNA and partial viral proteins were identified in purified exosomes isolated from FMDV-infected PK-15 cells with qRT-PCR and /MS. Exosomes from FMDV-infected cells were capable of transmitting infection to naive PK-15 cells and suckling mice. Furthermore, exosome-mediated infection cannot be fully blocked by FMDV-specific neutralizing antibodies. This finding highlights that FMDV transmission by exosomes as a potential immune evasion mechanism.


Assuntos
Exossomos/virologia , Vírus da Febre Aftosa/patogenicidade , Febre Aftosa/transmissão , Interações Hospedeiro-Patógeno , Evasão da Resposta Imune , Animais , Animais Recém-Nascidos , Anticorpos Neutralizantes , Exossomos/fisiologia , Vírus da Febre Aftosa/genética , Rim/citologia , Rim/virologia , Camundongos , Camundongos Endogâmicos C57BL , RNA Viral , Proteínas Virais/metabolismo
9.
Vet Microbiol ; 233: 174-183, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31176405

RESUMO

Bovine herpesvirus 1 (BHV-1) is an economically important pathogen of cattle and has led to significant consequences on the cattle industry worldwide. MicroRNAs (miRNAs) are a class of regulators that play critical roles in virus and host interaction. However, the roles of host miRNAs in BHV-1 infection remain largely unclear. In this study, a set of differentially expressed miRNAs by small RNA deep sequencing were analyzed in the Madin-Darby Bovine Kidney Cells (MDBK) infected with BHV-1 after 12 h, 24 h and 48 h post-infection compared to mock infection, and it was confirmed that bta-miR-2361 was significantly down-regulated. Moreover, bta-miR-2361 mimics transfection could inhibit BHV-1 replication. Combined with up-regulated genes from BHV-1-infected MDBK cells by deep RNA-sequencing and predicted by bioinformatics tools, early growth response 1 (EGR1) was putative target of bta-miR-2361. Furthermore, EGR1 was up-regulated during BHV-1 infection, and overexpression of EGR1 promoted BHV-1 replication whereas knockdown of EGR1 had the opposite effects. Subsequently, the target association between bta-miR-2361 and 3'UTR of EGR1 was further validated using a dual-luciferase reporter assay. In addition, overexpression of bta-miR-2361 resulted in decreased EGR1 mRNA and protein levels. Further mechanistic study showed that EGR1 stimulated BHV-1 UL46 promoter activity, but overexpression of bta-miR-2361 suppressed the production of UL46 gene. Collectively, this is the first study to reveal that bta-miR-2361 as a novel host factor regulates BHV-1 replication via directly targeting the EGR1 gene, which is a transcription factor that regulates viral UL46 gene of BHV-1. These results provide further insight into the study of BHV-1 pathogenesis.


Assuntos
Proteína 1 de Resposta de Crescimento Precoce/genética , Herpesvirus Bovino 1/fisiologia , MicroRNAs/genética , Replicação Viral , Animais , Bovinos , Linhagem Celular , Células Epiteliais , Regulação da Expressão Gênica , Herpesvirus Bovino 1/patogenicidade , Interações Hospedeiro-Patógeno , Regulação para Cima , Proteínas Virais/genética
10.
BMC Plant Biol ; 19(1): 239, 2019 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-31170918

RESUMO

BACKGROUND: Ammonium transporters (AMTs), a family of proteins transporting ammonium salt and its analogues, have been studied in many aspects. Although numerous studies have found that ammonium affects the interaction between plants and pathogens, the role of AMTs remains largely unknown, especially that of the AMT2-type AMTs. RESULTS: In the present study, we found that the concentration of ammonium in wheat leaves decreased after infection with Puccinia striiformis f. sp. tritici (Pst), the causal agent of stripe rust. Then, an AMT2-type ammonium transporter gene induced by Pst was identified and designated as TaAMT2;3a. Transient expression assays indicated that TaAMT2;3a was located to the cell and nuclear membranes. TaAMT2;3a successfully complemented the function of a yeast mutant defective in NH4+ transport, indicating its ammonium transport capacity. Function of TaAMT2;3a in wheat-Pst interaction was further analyzed by barley stripe mosaic virus (BSMV)-induced gene silencing. Pst growth was significantly retarded in TaAMT2;3a-knockdown plants, in which ammonium in leaves were shown to be induced at the early stage of infection. Histological observation showed that the hyphal length, the number of hyphal branches and haustorial mother cells decreased in the TaAMT2;3a knockdown plants, leading to the impeded growth of rust pathogens. CONCLUSIONS: The results clearly indicate that the induction of AMT2-type ammonium transporter gene TaAMT2;3a may facilitates the nitrogen uptake from wheat leaves by Pst, thereby contribute to the infection of rust fungi.


Assuntos
Basidiomycota/fisiologia , Proteínas de Transporte de Cátions/genética , Interações Hospedeiro-Patógeno , Doenças das Plantas/microbiologia , Proteínas de Plantas/genética , Triticum/genética , Triticum/microbiologia , Proteínas de Transporte de Cátions/metabolismo , Perfilação da Expressão Gênica , Regulação da Expressão Gênica de Plantas , Folhas de Planta/metabolismo , Proteínas de Plantas/metabolismo
11.
J Med Microbiol ; 68(7): 1096-1108, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31169490

RESUMO

PURPOSE: Extensively drug-resistant (XDR) strains of Acinetobacter baumannii are being reported worldwide, and they are associated with high morbidity and mortality rates. These strains are considered to be the highest priority for the development of new antibacterial agents. Therefore, we aimed to develop an effective alternative antimicrobial agent. METHODOLOGY: Bacteriophages (phages) were enriched and recovered from a hospital waste water sample after activated sludge treatment. The biological characteristics and therapeutic efficacy of the phages were evaluated in vitro and in vivo. RESULTS: Phage AB1801 was able to infect 70 % of XDR A. baumannii isolates and showed high pH, temperature and storage stability, with rapid adsorption (>80 % adsorbed in 10 min), a short latent period (20 min) and a large burst size (212 p.f.u./cell). The phage was classified as being in the order Caudovirales, family Siphoviridae. Phage AB1801 inhibited biofilm formation and reduced preformed biofilms in a dose-dependent manner. The prophylactic and therapeutic efficacy of AB1801 towards XDR A. baumannii infection was evaluated in Galleria mellonella larvae and the phage showed significant protective effects in both prophylactic and therapeutic treatment modalities. CONCLUSION: These studies suggest that phage AB1801 may be suitable for further development as an antimicrobial agent against XDR A. baumannii infection.


Assuntos
Acinetobacter baumannii/efeitos dos fármacos , Acinetobacter baumannii/virologia , Siphoviridae/fisiologia , Animais , Biofilmes , DNA Viral/genética , Farmacorresistência Bacteriana Múltipla , Interações Hospedeiro-Patógeno , Concentração de Íons de Hidrogênio , Larva/microbiologia , Microscopia Eletrônica de Varredura , Mariposas/microbiologia , Siphoviridae/genética , Siphoviridae/ultraestrutura , Temperatura Ambiente
13.
Nat Commun ; 10(1): 2727, 2019 06 21.
Artigo em Inglês | MEDLINE | ID: mdl-31227708

RESUMO

A fundamental challenge in medical microbiology is to characterize the dynamic protein-protein interaction networks formed at the host-pathogen interface. Here, we generate a quantitative interaction map between the significant human pathogen, Streptococcus pyogenes, and proteins from human saliva and plasma obtained via complementary affinity-purification and bacterial-surface centered enrichment strategies and quantitative mass spectrometry. Perturbation of the network using immunoglobulin protease cleavage, mixtures of different concentrations of saliva and plasma, and different S. pyogenes serotypes and their isogenic mutants, reveals how changing microenvironments alter the interconnectivity of the interaction map. The importance of host immunoglobulins for the interaction with human complement proteins is demonstrated and potential protective epitopes of importance for phagocytosis of S. pyogenes cells are localized. The interaction map confirms several previously described protein-protein interactions; however, it also reveals a multitude of additional interactions, with possible implications for host-pathogen interactions involving other bacterial species.


Assuntos
Anticorpos Antibacterianos/metabolismo , Proteínas de Bactérias/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Infecções Estreptocócicas/imunologia , Streptococcus pyogenes/imunologia , Anticorpos Antibacterianos/imunologia , Antígenos de Bactérias/imunologia , Antígenos de Bactérias/metabolismo , Proteínas de Bactérias/imunologia , Cromatografia de Afinidade , Proteínas do Sistema Complemento/imunologia , Proteínas do Sistema Complemento/metabolismo , Mapeamento de Epitopos , Voluntários Saudáveis , Humanos , Espectrometria de Massas , Proteínas Opsonizantes/imunologia , Proteínas Opsonizantes/metabolismo , Ligação Proteica , Mapeamento de Interação de Proteínas , Mapas de Interação de Proteínas/imunologia , Infecções Estreptocócicas/sangue , Infecções Estreptocócicas/microbiologia , Streptococcus pyogenes/metabolismo
14.
Nat Commun ; 10(1): 2699, 2019 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-31221976

RESUMO

Human cytomegalovirus (CMV) causes a wide array of disease to diverse populations of immune-compromised individuals. Thus, a more comprehensive understanding of how CMV enters numerous host cell types is necessary to further delineate the complex nature of CMV pathogenesis and to develop targeted therapeutics. To that end, we establish a vaccination strategy utilizing membrane vesicles derived from epithelial cells to generate a library of monoclonal antibodies (mAbs) targeting cell surface proteins in their native conformation. A high-throughput inhibition assay is employed to screen these antibodies for their ability to limit infection, and mAbs targeting CD46 are identified. In addition, a significant reduction of viral proliferation in CD46-KO epithelial cells confirms a role for CD46 function in viral dissemination. Further, we demonstrate a CD46-dependent entry pathway of virus infection in trophoblasts, but not in fibroblasts, highlighting the complexity of CMV entry and identifying CD46 as an entry factor in congenital infection.


Assuntos
Infecções por Citomegalovirus/imunologia , Citomegalovirus/imunologia , Interações Hospedeiro-Patógeno/imunologia , Proteína Cofatora de Membrana/imunologia , Internalização do Vírus , Anticorpos Monoclonais/administração & dosagem , Anticorpos Monoclonais/imunologia , Anticorpos Neutralizantes/administração & dosagem , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/administração & dosagem , Anticorpos Antivirais/imunologia , Linhagem Celular , Infecções por Citomegalovirus/prevenção & controle , Infecções por Citomegalovirus/virologia , Células Epiteliais/imunologia , Células Epiteliais/virologia , Fibroblastos/imunologia , Fibroblastos/virologia , Técnicas de Inativação de Genes , Humanos , Proteína Cofatora de Membrana/genética , RNA Interferente Pequeno/metabolismo , Trofoblastos/imunologia , Trofoblastos/virologia , Vacinas Virais/administração & dosagem , Vacinas Virais/imunologia
15.
BMC Bioinformatics ; 20(1): 297, 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31159726

RESUMO

BACKGROUND: Host factors of influenza virus replication are often found in key topological positions within protein-protein interaction networks. This work explores how protein states can be manipulated through controllability analysis: the determination of the minimum manipulation needed to drive the cell system to any desired state. Here, we complete a two-part controllability analysis of two protein networks: a host network representing the healthy cell state and an influenza A virus-host network representing the infected cell state. In this context, controllability analyses aim to identify key regulating host factors of the infected cell's progression. This knowledge can be utilized in further biological analysis to understand disease dynamics and isolate proteins for study as drug target candidates. RESULTS: Both topological and controllability analyses provide evidence of wide-reaching network effects stemming from the addition of viral-host protein interactions. Virus interacting and driver host proteins are significant both topologically and in controllability, therefore playing important roles in cell behavior during infection. Functional analysis finds overlap of results with previous siRNA studies of host factors involved in influenza replication, NF-kB pathway and infection relevance, and roles as interferon regulating genes. 24 proteins are identified as holding regulatory roles specific to the infected cell by measures of topology, controllability, and functional role. These proteins are recommended for further study as potential antiviral drug targets. CONCLUSIONS: Seasonal outbreaks of influenza A virus are a major cause of illness and death around the world each year with a constant threat of pandemic infection. This research aims to increase the efficiency of antiviral drug target discovery using existing protein-protein interaction data and network analysis methods. These results are beneficial to future studies of influenza virus, both experimental and computational, and provide evidence that the combination of topology and controllability analyses may be valuable for future efforts in drug target discovery.


Assuntos
Antivirais/farmacologia , Sistemas de Liberação de Medicamentos , Descoberta de Drogas , Interações Hospedeiro-Patógeno , Mapas de Interação de Proteínas , Humanos , Vírus da Influenza A/efeitos dos fármacos , Vírus da Influenza A/metabolismo , RNA Interferente Pequeno/metabolismo , Reprodutibilidade dos Testes , Replicação Viral/efeitos dos fármacos
16.
Acta Virol ; 63(2): 195-202, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31230448

RESUMO

The 1918 "Spanish" pandemic is the earliest known influenza H1N1 virus. Since then H1N1 viruses circulated between humans and animals continuously. With the increased amount of samples of H1N1 viruses and technology development, researchers have been studying how the viruses evolved. Here, we analyzed HA and NA genes of H1N1 viruses from three aspects: host distribution, geographical distribution and phylogenetic analysis. The data showed hosts were predominantly human, swine and poultry, and other hosts were mainly cat, ferret, wild bear, canine, cheetah and seal. In terms of geographical distribution, the North America and Eurasia were the main H1N1 influenza pandemic areas. Of them, the United States, China, Japan, Canada, the United Kingdom, India and Singapore were the most affected. The phylogenetic analysis of surface genes of influenza H1N1 viruses from 1918 to 2017 worldwide revealed the distribution of all avian influenza viruses (AIVs) showed a clear geographical difference, mainly concentrated in Eurasia and America. American and Eurasian swine viruses might be the ancestors of the 2009 pandemic virus' HA and NA genes. Swine influenza viruses played an important role in the spread of influenza viruses across species. To our knowledge, this is the first large-scale phylogenetic analysis of HA and NA genes of influenza H1N1 viruses worldwide until now. Our findings further emphasize the importance of surveillance of the genetic diversity of influenza H1N1 viruses in different hosts and raised more concerns about the long-time monitoring. Keywords: influenza H1N1 viruses; HA genes; NA genes; phylogenetic analysis; evolution.


Assuntos
Vírus da Influenza A Subtipo H1N1 , Infecções por Orthomyxoviridae , Filogenia , Animais , Gatos , China , Cães , Interações Hospedeiro-Patógeno , Humanos , Índia , Vírus da Influenza A Subtipo H1N1/classificação , Vírus da Influenza A Subtipo H1N1/genética , Influenza Humana/virologia , Infecções por Orthomyxoviridae/virologia , Suínos
17.
Mol Plant Microbe Interact ; 32(8): 1038-1046, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31237473

RESUMO

Pattern-triggered immunity is an inherent feature of the plant immune system. Recognition of either microbe-derived surface structures (patterns) or of plant materials released due to the deleterious impact of microbial infection is brought about by plasma membrane pattern recognition receptors (PRRs). PRRs composed of leucine-rich repeat (LRR) ectodomains are thought to mediate sensing of proteinaceous patterns and to initiate signaling cascades culminating in the activation of generic plant defenses. In contrast to LRR receptor kinases, LRR receptor proteins (LRR-RPs) lack a cytoplasmic kinase domain for initiation of downstream signal transduction. LRR-RPs form heteromeric constitutive, ligand-independent complexes with coreceptor SOBIR1. Upon ligand binding to LRR-RPs, recruitment of coreceptor SERK3/BAK1 results in formation of a ternary PRR complex. Structure-function analysis of LRR-RP-type PRRs is missing. AtRLP23 constitutes an LRR-RP PRR that mediates recognition of a peptide motif (nlp20) found in numerous bacterial, fungal, and oomycete necrosis and ethylene-inducing peptide 1-like proteins (NLPs). We here report the use of a series of AtRLP23 variants to decipher subdomains required for ligand binding and interaction with coreceptors AtSOBIR1 and AtBAK1, respectively. Deletion of LRR1 or LRR3 subdomains efficiently abrogated the ability of AtRLP23 receptor variants to confer nlp20 pattern sensitivity, to bind nlp20, and to recruit AtBAK1 into a ternary PRR complex. This suggests that the very N-terminal part of the AtRLP23 ectodomain is crucial for receptor function. Deletion of the intracellular 17-amino-acid tail of AtRLP23 reduced but did not abolish receptor function, suggesting an auxiliary role of this domain in receptor function. We further found that interaction of AtRLP23 and other LRR-RP-type PRRs with AtSOBIR1 does not require the AtRLP23 LRR ectodomain but is brought about by a GxxxG protein dimerization motif in the transmembrane domain and a stretch of negatively charged glutamic acid residues in the outer juxtamembrane domain of the receptor. Further, AtRLP23 levels were found to be unaltered in Atsobir1-1 mutant genotypes, suggesting that AtSOBIR1 does not act as a protein scaffold in stabilizing LRR-RP-type PRRs in Arabidopsis.


Assuntos
Proteínas de Arabidopsis , Arabidopsis , Interações Hospedeiro-Patógeno , Receptores de Reconhecimento de Padrão , Arabidopsis/genética , Arabidopsis/imunologia , Proteínas de Arabidopsis/química , Proteínas de Arabidopsis/genética , Proteínas de Arabidopsis/metabolismo , Ligantes , Receptores de Reconhecimento de Padrão/química , Receptores de Reconhecimento de Padrão/genética , Receptores de Reconhecimento de Padrão/metabolismo , Transdução de Sinais , Relação Estrutura-Atividade
18.
J Agric Food Chem ; 67(27): 7738-7747, 2019 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-31199650

RESUMO

Cytosinpeptidemycin (CytPM) is a microbial pesticide that displayed broad-spectrum antiviral activity against various plant viruses. However, the molecular mechanism underlying antiviral activity of CytPM is poorly understood. In this study, the results demonstrated that CytPM could effectively delay the systemic infection of tobacco mosaic virus (TMV) in Nicotiana benthamiana and significantly inhibit the viral accumulation in tobacco BY-2 protoplasts. Results of RNA-seq indicated that 210 and 120 differential expressed genes (DEGs) were significantly up- and down-regulated after CytPM treatment in BY-2 protoplasts, respectively. In addition, KEGG analysis indicated that various DEGs were involved in endoplasmic reticulum (ER) protein processing, suggesting a possible correlation between ER homeostasis and virus resistance. RT-qPCR was performed to validate the gene expression of crucial DEGs related with defense, stress responses, signaling transduction, and phytohormone, which were consistent with results of RNA-seq. Our works provided valuable insights into the antiviral mechanism of CytPM that induced host resistance to viral infection.


Assuntos
Antivirais , Citosina/análogos & derivados , Resistência à Doença/genética , Doenças das Plantas/prevenção & controle , Vírus do Mosaico do Tabaco/fisiologia , Tabaco/virologia , Citosina/farmacologia , Resistência à Doença/efeitos dos fármacos , Expressão Gênica , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Interações Hospedeiro-Patógeno/efeitos dos fármacos , Interações Hospedeiro-Patógeno/genética , Doenças das Plantas/virologia , Reguladores de Crescimento de Planta/genética , Protoplastos/efeitos dos fármacos , Protoplastos/virologia , Transdução de Sinais/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Estresse Fisiológico/genética , Tabaco/genética , Vírus do Mosaico do Tabaco/efeitos dos fármacos , Vírus do Mosaico do Tabaco/patogenicidade
19.
Virol J ; 16(1): 73, 2019 05 30.
Artigo em Inglês | MEDLINE | ID: mdl-31146743

RESUMO

BACKGROUND: The ubiquitin proteasome system (UPS) regulates the expression levels of cellular proteins by ubiquitination of protein substrates followed by their degradation via the proteasome. As a highly conserved cellular degradation mechanism, the UPS affects a variety of biological processes and participates in viral propagation. MAIN BODY: During hepatitis B virus (HBV) infection, the UPS is shown to act as a double-edged sword in viral pathogenesis. On the one hand, the UPS acts as a host defense mechanism to selectively recognize HBV proteins as well as special cellular proteins that favor the viral life cycle and induces their ubiquitin-dependent proteasomal degradation to limit HBV infection. On the other hand, the HBV has evolved to subvert the UPS function for its own advantage. Moreover, in the infected hepatocytes, certain cellular proteins that are dependent on the UPS are involved in abnormal biological processes which are mediated by HBV. CONCLUSION: The molecular interaction of HBV with the UPS to modulate viral propagation and pathogenesis is summarized in the review. Considering the important role of the UPS in HBV infection, a better understanding of the HBV-UPS interaction could provide novel insight into the mechanisms that are involved in viral replication and pathogenesis and help to develop potential treatment strategies targeting the UPS.


Assuntos
Vírus da Hepatite B/patogenicidade , Interações Hospedeiro-Patógeno , Complexo de Endopeptidases do Proteassoma/metabolismo , Replicação Viral , Animais , Hepatite B/patologia , Vírus da Hepatite B/fisiologia , Hepatócitos/virologia , Humanos , Camundongos , Ubiquitinação
20.
Nat Commun ; 10(1): 2830, 2019 06 27.
Artigo em Inglês | MEDLINE | ID: mdl-31249303

RESUMO

Cytomegalovirus is a DNA-encoded ß-herpesvirus that induces STING-dependent type 1 interferon responses in macrophages and uses myeloid cells as a vehicle for dissemination. Here we report that STING knockout mice are as resistant to murine cytomegalovirus (MCMV) infection as wild-type controls, whereas mice with a combined Toll-like receptor/RIG-I-like receptor/STING signaling deficiency do not mount type 1 interferon responses and succumb to the infection. Although STING alone is dispensable for survival, early IFN-ß induction in Kupffer cells is STING-dependent and controls early hepatic virus propagation. Infection experiments with an inducible reporter MCMV show that STING constrains MCMV replication in myeloid cells and limits viral dissemination via these cells. By contrast, restriction of viral dissemination from hepatocytes to other organs is independent of STING. Thus, during MCMV infection STING is involved in early IFN-ß induction in Kupffer cells and the restriction of viral dissemination via myeloid cells, whereas it is dispensable for survival.


Assuntos
Infecções por Herpesviridae/veterinária , Interferon beta/metabolismo , Fígado/metabolismo , Proteínas de Membrana/metabolismo , Muromegalovirus/fisiologia , Células Mieloides/metabolismo , Doenças dos Roedores/metabolismo , Animais , Feminino , Hepatócitos/metabolismo , Hepatócitos/virologia , Infecções por Herpesviridae/virologia , Interações Hospedeiro-Patógeno , Interferon beta/genética , Macrófagos do Fígado/metabolismo , Macrófagos do Fígado/virologia , Fígado/virologia , Masculino , Proteínas de Membrana/genética , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Muromegalovirus/genética , Células Mieloides/virologia , Doenças dos Roedores/genética , Doenças dos Roedores/virologia , Transdução de Sinais , Receptores Toll-Like/genética , Receptores Toll-Like/metabolismo
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