Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 273
Filtrar
1.
Nature ; 554(7690): 118-122, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29364876

RESUMO

The most abundant viruses on Earth are thought to be double-stranded DNA (dsDNA) viruses that infect bacteria. However, tailed bacterial dsDNA viruses (Caudovirales), which dominate sequence and culture collections, are not representative of the environmental diversity of viruses. In fact, non-tailed viruses often dominate ocean samples numerically, raising the fundamental question of the nature of these viruses. Here we characterize a group of marine dsDNA non-tailed viruses with short 10-kb genomes isolated during a study that quantified the diversity of viruses infecting Vibrionaceae bacteria. These viruses, which we propose to name the Autolykiviridae, represent a novel family within the ancient lineage of double jelly roll (DJR) capsid viruses. Ecologically, members of the Autolykiviridae have a broad host range, killing on average 34 hosts in four Vibrio species, in contrast to tailed viruses which kill on average only two hosts in one species. Biochemical and physical characterization of autolykiviruses reveals multiple virion features that cause systematic loss of DJR viruses in sequencing and culture-based studies, and we describe simple procedural adjustments to recover them. We identify DJR viruses in the genomes of diverse major bacterial and archaeal phyla, and in marine water column and sediment metagenomes, and find that their diversity greatly exceeds the diversity that is currently captured by the three recognized families of such viruses. Overall, these data suggest that viruses of the non-tailed dsDNA DJR lineage are important but often overlooked predators of bacteria and archaea that impose fundamentally different predation and gene transfer regimes on microbial systems than on tailed viruses, which form the basis of all environmental models of bacteria-virus interactions.


Assuntos
Organismos Aquáticos/virologia , Bactérias/virologia , Vírus de DNA/classificação , Vírus de DNA/patogenicidade , Filogenia , Archaea/virologia , Viés , Proteínas do Capsídeo/metabolismo , Vírus de DNA/genética , Vírus de DNA/isolamento & purificação , Metagenômica , Vibrio/virologia
2.
Proc Natl Acad Sci U S A ; 118(2)2021 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-33443221

RESUMO

Reston virus (RESTV), an ebolavirus, causes clinical disease in macaques but has yet only been associated with rare asymptomatic infections in humans. Its 2008 emergence in pigs in the Philippines raised concerns about food safety, pathogenicity, and zoonotic potential, questions that are still unanswered. Until today, the virulence of RESTV for pigs has remained elusive, with unclear pathogenicity in naturally infected animals and only one experimental study demonstrating susceptibility and evidence for shedding but no disease. Here we show that combined oropharyngeal and nasal infection of young (3- to 7-wk-old) Yorkshire cross pigs with RESTV resulted in severe respiratory disease, with most animals reaching humane endpoint within a week. RESTV-infected pigs developed severe cyanosis, tachypnea, and acute interstitial pneumonia, with RESTV shedding from oronasal mucosal membranes. Our studies indicate that RESTV should be considered a livestock pathogen with zoonotic potential.


Assuntos
Ebolavirus/imunologia , Insuficiência Respiratória/virologia , Doenças dos Suínos/virologia , Animais , Anticorpos Antivirais/imunologia , Causalidade , Vírus de DNA/patogenicidade , Surtos de Doenças/prevenção & controle , Ebolavirus/metabolismo , Ebolavirus/patogenicidade , Filipinas/epidemiologia , Insuficiência Respiratória/veterinária , Sus scrofa/virologia , Suínos/virologia , Doenças dos Suínos/epidemiologia , Eliminação de Partículas Virais/imunologia
3.
J Biol Chem ; 297(1): 100856, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34097873

RESUMO

The nuclear pore complex is the sole gateway connecting the nucleoplasm and cytoplasm. In humans, the nuclear pore complex is one of the largest multiprotein assemblies in the cell, with a molecular mass of ∼110 MDa and consisting of 8 to 64 copies of about 34 different nuclear pore proteins, termed nucleoporins, for a total of 1000 subunits per pore. Trafficking events across the nuclear pore are mediated by nuclear transport receptors and are highly regulated. The nuclear pore complex is also used by several RNA viruses and almost all DNA viruses to access the host cell nucleoplasm for replication. Viruses hijack the nuclear pore complex, and nuclear transport receptors, to access the nucleoplasm where they replicate. In addition, the nuclear pore complex is used by the cell innate immune system, a network of signal transduction pathways that coordinates the first response to foreign invaders, including viruses and other pathogens. Several branches of this response depend on dynamic signaling events that involve the nuclear translocation of downstream signal transducers. Mounting evidence has shown that these signaling cascades, especially those steps that involve nucleocytoplasmic trafficking events, are targeted by viruses so that they can evade the innate immune system. This review summarizes how nuclear pore proteins and nuclear transport receptors contribute to the innate immune response and highlights how viruses manipulate this cellular machinery to favor infection. A comprehensive understanding of nuclear pore proteins in antiviral innate immunity will likely contribute to the development of new antiviral therapeutic strategies.


Assuntos
Imunidade Inata/genética , Complexo de Proteínas Formadoras de Poros Nucleares/genética , Poro Nuclear/genética , Viroses/genética , Transporte Ativo do Núcleo Celular/genética , Transporte Ativo do Núcleo Celular/imunologia , Vírus de DNA/genética , Vírus de DNA/patogenicidade , Humanos , Evasão da Resposta Imune/genética , Evasão da Resposta Imune/imunologia , NF-kappa B/genética , Poro Nuclear/imunologia , Complexo de Proteínas Formadoras de Poros Nucleares/imunologia , Vírus de RNA/genética , Vírus de RNA/patogenicidade , Proteínas não Estruturais Virais/genética , Viroses/imunologia , Viroses/virologia , Replicação Viral/genética , Replicação Viral/imunologia
4.
Nat Immunol ; 11(5): 395-402, 2010 May.
Artigo em Inglês | MEDLINE | ID: mdl-20351692

RESUMO

Inflammasomes regulate the activity of caspase-1 and the maturation of interleukin 1beta (IL-1beta) and IL-18. AIM2 has been shown to bind DNA and engage the caspase-1-activating adaptor protein ASC to form a caspase-1-activating inflammasome. Using Aim2-deficient mice, we identify a central role for AIM2 in regulating caspase-1-dependent maturation of IL-1beta and IL-18, as well as pyroptosis, in response to synthetic double-stranded DNA. AIM2 was essential for inflammasome activation in response to Francisella tularensis, vaccinia virus and mouse cytomegalovirus and had a partial role in the sensing of Listeria monocytogenes. Moreover, production of IL-18 and natural killer cell-dependent production of interferon-gamma, events critical in the early control of virus replication, were dependent on AIM2 during mouse cytomegalovirus infection in vivo. Collectively, our observations demonstrate the importance of AIM2 in the sensing of both bacterial and viral pathogens and in triggering innate immunity.


Assuntos
Infecções por Vírus de DNA/imunologia , Vírus de DNA/imunologia , Francisella tularensis/imunologia , Células Matadoras Naturais/metabolismo , Listeriose/imunologia , Macrófagos/metabolismo , Complexos Multiproteicos/metabolismo , Proteínas Nucleares/metabolismo , Tularemia/imunologia , Animais , Proteínas Reguladoras de Apoptose , Proteínas Adaptadoras de Sinalização CARD , Caspase 1/genética , Caspase 1/imunologia , Caspase 1/metabolismo , Linhagem Celular , Citocinas/genética , Citocinas/imunologia , Citocinas/metabolismo , Proteínas do Citoesqueleto/genética , DNA/imunologia , Infecções por Vírus de DNA/genética , Infecções por Vírus de DNA/metabolismo , Vírus de DNA/crescimento & desenvolvimento , Vírus de DNA/patogenicidade , Proteínas de Ligação a DNA , Francisella tularensis/patogenicidade , Humanos , Imunidade Inata , Células Matadoras Naturais/imunologia , Células Matadoras Naturais/microbiologia , Células Matadoras Naturais/patologia , Células Matadoras Naturais/virologia , Listeriose/genética , Listeriose/metabolismo , Ativação Linfocitária/genética , Macrófagos/imunologia , Macrófagos/microbiologia , Macrófagos/patologia , Macrófagos/virologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Complexos Multiproteicos/genética , Complexos Multiproteicos/imunologia , Proteínas Nucleares/genética , Proteínas Nucleares/imunologia , Transdução de Sinais/genética , Transdução de Sinais/imunologia , Fatores de Transcrição/genética , Fatores de Transcrição/imunologia , Fatores de Transcrição/metabolismo , Tularemia/genética , Tularemia/metabolismo , Carga Viral/genética , Carga Viral/imunologia
5.
J Gen Virol ; 102(1)2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-33258767

RESUMO

Viruses in the family Redondoviridae have a circular genome of 3.0 kb with three open reading frames. The packaged genome is inferred to be single-stranded DNA by analogy to related viruses. Redondoviruses were discovered through metagenomic sequencing methods in samples from human subjects and are inferred to replicate in humans. Evidence of redondovirus infection is associated with periodontitis and critical illness, but redondoviruses have not been shown to be the causative agent of any diseases. This is a summary of the International Committee on Taxonomy of Viruses (ICTV) Report on the family Redondoviridae, which is available at ictv.global/report/redondoviridae.


Assuntos
Vírus de DNA/classificação , Vírus de DNA/genética , Vírus de DNA/patogenicidade , Vírus de DNA/fisiologia , DNA Circular , DNA de Cadeia Simples , DNA Viral , Genoma Viral/genética , Humanos , Metagenômica , Fases de Leitura Aberta , Replicação Viral
6.
J Invertebr Pathol ; 184: 107636, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34116033

RESUMO

The spread, emergence, and adaptation of pathogens causing marine disease has been problematic to fisheries and aquaculture industries for the last several decades creating the need for strategic management and biosecurity practices. The Pacific oyster (Crassostrea gigas), a highly productive species globally, has been a target of disease and mortality caused by a viral pathogen, the Ostreid herpesvirus 1 (OsHV-1) and its microvariants (OsHV-1 µvars). During routine surveillance to establish health history at a shellfish aquaculture nursery system in San Diego, California, the presence of OsHV-1 in Pacific oyster juveniles was detected. Quantification of OsHV-1 in tissues of oysters revealed OsHV-1 viral loads > 106 copies/mg. We characterized and identified the OsHV-1 variant by sequencing of ORFs 4 (C2/C6) and 43 (IA1/IA2), which demonstrated that this variant is a novel OsHV-1 microvariant: OsHV-1 µvar SD. A pilot transmission study indicates that OsHV-1 µvar SD is infectious with high viral loads ~ 7.57 × 106 copies/mg detected in dead individuals. The detection of OsHV-1 µvar SD in a large port mirrors previous studies conducted in Australia where aquaculture farms and feral populations near port locations may be at a higher risk of OsHV-1 emergence. Further research is needed to understand the impacts of OsHV-1 µvar SD, such as transmission studies focusing on potential vectors and characterization of virulence as compared to other OsHV-1 µvars. To increase biosecurity of the global aquaculture industry, active and passive surveillance may be necessary to reduce spread of pathogens and make appropriate management decisions.


Assuntos
Crassostrea/virologia , Vírus de DNA/isolamento & purificação , Animais , California , Vírus de DNA/genética , Vírus de DNA/patogenicidade , Carga Viral , Virulência
7.
J Fish Dis ; 44(11): 1811-1818, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34324718

RESUMO

Recently, the culture of American eels (Anguilla rostrate) in China has been impacted by emergence of a disease with signs of haemorrhagic gill necrosis. The gills of diseased eels are covered with petecchia and they bleed when the operculum is pressed. In this study, a novel American eel adomavirus (AEAdoV) was isolated from the diseased eels using the eel ovary cell line (EO). The virus proliferated in the EO cells with a maximum TCID50 /ml of 106.29 ± 0.23 at 6 days post-infection. The virions were non-enveloped with a diameter of 75-85 nm and shown to be a DNA virus upon 5-iodo-2'-deoxyuridine (IDU) treatment. PCR assays showed that AEAdoV encodes a superfamily 3 helicases (S3H) replicase and shared high similarities with Anguilla marmorata adomavirus (MEAdoV). Although no clinical signs or mortality was observed among the eels injected with AEAdoV, the virus was reisolated from livers, kidneys and gills of injected eels at 35 days post-injection. Our results suggested that AEAdoV exhibited a latent infection in A. rostrata. The pathogenicity of the AEAdoV needs to be confirmed further.


Assuntos
Anguilla/virologia , Vírus de DNA/classificação , Doenças dos Peixes/virologia , Necrose/veterinária , Animais , Aquicultura , China , Vírus de DNA/isolamento & purificação , Vírus de DNA/patogenicidade , Brânquias/patologia , Brânquias/virologia , Necrose/virologia , Filogenia
8.
Int J Mol Sci ; 22(18)2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34575975

RESUMO

Several classes of immunomodulators are used for treating relapsing-remitting multiple sclerosis (RRMS). Most of these disease-modifying therapies, except teriflunomide, carry the risk of progressive multifocal leukoencephalopathy (PML), a severely debilitating, often fatal virus-induced demyelinating disease. Because teriflunomide has been shown to have antiviral activity against DNA viruses, we investigated whether treatment of cells with teriflunomide inhibits infection and spread of JC polyomavirus (JCPyV), the causative agent of PML. Treatment of choroid plexus epithelial cells and astrocytes with teriflunomide reduced JCPyV infection and spread. We also used droplet digital PCR to quantify JCPyV DNA associated with extracellular vesicles isolated from RRMS patients. We detected JCPyV DNA in all patients with confirmed PML diagnosis (n = 2), and in six natalizumab-treated (n = 12), two teriflunomide-treated (n = 7), and two nonimmunomodulated (n = 2) patients. Of the 21 patients, 12 (57%) had detectable JCPyV in either plasma or serum. CSF was uniformly negative for JCPyV. Isolation of extracellular vesicles did not increase the level of detection of JCPyV DNA versus bulk unprocessed biofluid. Overall, our study demonstrated an effect of teriflunomide inhibiting JCPyV infection and spread in glial and choroid plexus epithelial cells. Larger studies using patient samples are needed to correlate these in vitro findings with patient data.


Assuntos
Crotonatos/farmacologia , Vírus de DNA/efeitos dos fármacos , Hidroxibutiratos/farmacologia , Leucoencefalopatia Multifocal Progressiva/tratamento farmacológico , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Neuroglia/efeitos dos fármacos , Nitrilas/farmacologia , Toluidinas/farmacologia , Astrócitos/efeitos dos fármacos , Astrócitos/virologia , Linhagem Celular , Plexo Corióideo/efeitos dos fármacos , Plexo Corióideo/virologia , Vírus de DNA/patogenicidade , Doenças Desmielinizantes/tratamento farmacológico , Doenças Desmielinizantes/patologia , Doenças Desmielinizantes/virologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/virologia , Vesículas Extracelulares/efeitos dos fármacos , Vesículas Extracelulares/virologia , Humanos , Fatores Imunológicos/efeitos adversos , Fatores Imunológicos/uso terapêutico , Vírus JC/efeitos dos fármacos , Vírus JC/patogenicidade , Leucoencefalopatia Multifocal Progressiva/induzido quimicamente , Leucoencefalopatia Multifocal Progressiva/patologia , Leucoencefalopatia Multifocal Progressiva/virologia , Esclerose Múltipla Recidivante-Remitente/genética , Esclerose Múltipla Recidivante-Remitente/patologia , Esclerose Múltipla Recidivante-Remitente/virologia , Neuroglia/virologia , Viroses/tratamento farmacológico , Viroses/genética , Viroses/virologia
9.
BMC Genomics ; 21(1): 620, 2020 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-32912133

RESUMO

BACKGROUND: Since 2008, the aquaculture production of Crassostrea gigas was heavily affected by mass mortalities associated to Ostreid herpesvirus 1 (OsHV-1) microvariants worldwide. Transcriptomic studies revealed the major antiviral pathways of the oyster immune response while other findings suggested that also small non-coding RNAs (sncRNA) such as microRNAs might act as key regulators of the oyster response against OsHV-1. To explore the explicit connection between small non-coding and protein-coding transcripts, we performed paired whole transcriptome analysis of sncRNA and messenger RNA (mRNA) in six oysters selected for different intensities of OsHV-1 infection. RESULTS: The mRNA profiles of the naturally infected oysters were mostly governed by the transcriptional activity of OsHV-1, with several differentially expressed genes mapping to the interferon, toll, apoptosis, and pro-PO pathways. In contrast, miRNA profiles suggested more complex regulatory mechanisms, with 15 differentially expressed miRNAs (DE-miRNA) pointing to a possible modulation of the host response during OsHV-1 infection. We predicted 68 interactions between DE-miRNAs and oyster 3'-UTRs, but only few of them involved antiviral genes. The sncRNA reads assigned to OsHV-1 rather resembled mRNA degradation products, suggesting the absence of genuine viral miRNAs. CONCLUSIONS: We provided data describing the miRNAome during OsHV-1 infection in C. gigas. This information can be used to understand the role of miRNAs in healthy and diseased oysters, to identify new targets for functional studies and, eventually to disentangle cause and effect relationships during viral infections in marine mollusks.


Assuntos
Crassostrea/genética , Redes Reguladoras de Genes , MicroRNAs/genética , RNA Mensageiro/genética , Animais , Crassostrea/virologia , Vírus de DNA/patogenicidade , Resistência à Doença , MicroRNAs/metabolismo , RNA Mensageiro/metabolismo , Transcriptoma
10.
J Gen Virol ; 101(6): 651-666, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32391748

RESUMO

Crangon crangon is economically a very important species. Recently, promising culture attempts have been made, but a major problem is the uncontrollable mortality during the grow-out phase. As of yet, the life cycle of C. crangon is not closed in captivity so wild-caught individuals are used for further rearing. Therefore, it is important to investigate the virome of C. crangon both in wild-caught animals as in cultured animals. In recent years, next-generation-sequencing (NGS) technologies have been very important in the unravelling of the virome of a wide range of environments and matrices, such as soil, sea, potable water, but also of a wide range of animal species. This will be the first report of a virome study in C. crangon using NGS in combination with the NetoVIR protocol. The near complete genomes of 16 novel viruses were described, most of which were rather distantly related to unclassified viruses or viruses belonging to the Picornavirales, Bunyavirales Nudiviridae, Parvoviridae, Flaviviridae, Hepeviridae, Tombusviridae, Narnaviridae, Nodaviridae, Sobemovirus. A difference in virome composition was observed between muscle and hepatopancreatic tissue, suggesting a distinct tissue tropism of several of these viruses. Some differences in the viral composition were noted between the cultured and wild shrimp, which could indicate that in sub-optimal aquaculture conditions some viruses become more abundant. This research showed that a plethora of unknown viruses is present in C. crangon and that more research is needed to determine which virus is potentially dangerous for the culture of C. crangon.


Assuntos
Crangonidae/virologia , Vírus de DNA/patogenicidade , Animais , Aquicultura , Penaeidae/virologia
11.
J Mol Evol ; 88(1): 41-56, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31599342

RESUMO

Viruses have been infecting their host cells since the dawn of life, and this extremely long-term coevolution gave rise to some surprising consequences for the entire tree of life. It is hypothesised that viruses might have contributed to the formation of the first cellular life form, or that even the eukaryotic cell nucleus originates from an infection by a coated virus. The continuous struggle between viruses and their hosts to maintain at least a constant fitness level led to the development of an unceasing arms race, where weapons are often shuttled between the participants. In this literature review we try to give a short insight into some general consequences or traits of virus-host coevolution, and after this we zoom in to the viral clades of adenoviruses, herpesviruses, nucleo-cytoplasmic large DNA viruses, polyomaviruses and, finally, circoviruses.


Assuntos
Interações entre Hospedeiro e Microrganismos/genética , Interações entre Hospedeiro e Microrganismos/fisiologia , Vírus/genética , Adaptação Fisiológica/genética , Animais , Evolução Biológica , Vírus de DNA/genética , Vírus de DNA/patogenicidade , Evolução Molecular , Humanos , Vírus/patogenicidade
12.
PLoS Pathog ; 14(10): e1007336, 2018 10.
Artigo em Inglês | MEDLINE | ID: mdl-30321235

RESUMO

MITA (also called STING) is a central adaptor protein in innate immune response to cytosolic DNA. Cellular trafficking of MITA from the ER to perinuclear microsomes after DNA virus infection is critical for MITA activation and onset of innate antiviral response. Here we found that SNX8 is a component of DNA-triggered induction of downstream effector genes and innate immune response. Snx8-/- mice infected with the DNA virus HSV-1 exhibited lower serum cytokine levels and higher viral titers in the brains, resulting in higher lethality. Mechanistically, SNX8 recruited the class III phosphatylinositol 3-kinase VPS34 to MITA, which is required for trafficking of MITA from the ER to perinuclear microsomes. Our findings suggest that SNX8 is a critical component in innate immune response to cytosolic DNA and DNA virus.


Assuntos
Encéfalo/imunologia , Infecções por Vírus de DNA/imunologia , Vírus de DNA/patogenicidade , Imunidade Inata/imunologia , Proteínas de Membrana/metabolismo , Nexinas de Classificação/fisiologia , Animais , Encéfalo/patologia , Encéfalo/virologia , Citocinas/metabolismo , Infecções por Vírus de DNA/metabolismo , Infecções por Vírus de DNA/virologia , Vírus de DNA/imunologia , Células HEK293 , Células HeLa , Humanos , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Transporte Proteico , Carga Viral
13.
Virol J ; 17(1): 119, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32738914

RESUMO

BACKGROUND: Acute respiratory infections are a common disease in children with high mortality and morbidity. Multiple pathogens can cause acute respiratory infections. A 2-year survey of hospitalized children was conducted to understand the epidemic situation, seasonal spread of pathogens and the improvement of clinical diagnosis, treatment and prevention of disease in Huzhou, China. METHODS: From September 2017 to August 2019, 3121 nasopharyngeal swabs from hospitalized children with acute respiratory infections were collected, and real-time PCR was used to detect various pathogens. Then, pathogen profiles, frequency and seasonality were analyzed. RESULTS: Of the 3121 specimens, 14.45% (451/3121) were positive for at least one pathogen. Of the single-pathogen infections, RSV (45.61%, 182/399) was the most frequent pathogen, followed by PIVs (14.79%, 59/399), ADV (14.54%, 58/399), MP (10.78%, 43/399), and IAV (5.26%, 21/399). Of the 52 coinfections, RSV + PIVs viruses were predominantly identified and accounted for 40.38% (21/52) of cases. RSV was the most frequent pathogen in all four groups. The highest positive rate of the pathogens occurred in the winter (21.26%), followed by autumn (14.98%), the summer (14.11%) and the spring (12.25%). CONCLUSION: Viruses are the main pathogens in hospitalized children with acute respiratory infections in Huzhou city, Zhejiang Province, China. Among the pathogens, RSV had the highest detection rate, and MP is also a common pathogen among children with acute respiratory infections. This study provided a better understanding of the distribution of pathogens in children of different ages and seasons, which is conducive to the development of more reasonable treatment strategies and prevention and control measures.


Assuntos
Infecções por Chlamydophila/epidemiologia , Infecções por Vírus de DNA/epidemiologia , Vírus de DNA/patogenicidade , Pneumonia por Mycoplasma/epidemiologia , Infecções Respiratórias/microbiologia , Infecções Respiratórias/virologia , Doença Aguda/epidemiologia , Adolescente , Criança , Pré-Escolar , China/epidemiologia , Chlamydophila pneumoniae/genética , Chlamydophila pneumoniae/patogenicidade , Coinfecção/microbiologia , Coinfecção/virologia , Vírus de DNA/genética , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Masculino , Mycoplasma pneumoniae/genética , Mycoplasma pneumoniae/patogenicidade , Infecções por Vírus Respiratório Sincicial/epidemiologia , Vírus Sinciciais Respiratórios/genética , Vírus Sinciciais Respiratórios/patogenicidade , Infecções Respiratórias/epidemiologia , Estações do Ano
14.
Nature ; 505(7485): 691-5, 2014 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-24284630

RESUMO

The type I interferon (IFN) response protects cells from viral infection by inducing hundreds of interferon-stimulated genes (ISGs), some of which encode direct antiviral effectors. Recent screening studies have begun to catalogue ISGs with antiviral activity against several RNA and DNA viruses. However, antiviral ISG specificity across multiple distinct classes of viruses remains largely unexplored. Here we used an ectopic expression assay to screen a library of more than 350 human ISGs for effects on 14 viruses representing 7 families and 11 genera. We show that 47 genes inhibit one or more viruses, and 25 genes enhance virus infectivity. Comparative analysis reveals that the screened ISGs target positive-sense single-stranded RNA viruses more effectively than negative-sense single-stranded RNA viruses. Gene clustering highlights the cytosolic DNA sensor cyclic GMP-AMP synthase (cGAS, also known as MB21D1) as a gene whose expression also broadly inhibits several RNA viruses. In vitro, lentiviral delivery of enzymatically active cGAS triggers a STING-dependent, IRF3-mediated antiviral program that functions independently of canonical IFN/STAT1 signalling. In vivo, genetic ablation of murine cGAS reveals its requirement in the antiviral response to two DNA viruses, and an unappreciated contribution to the innate control of an RNA virus. These studies uncover new paradigms for the preferential specificity of IFN-mediated antiviral pathways spanning several virus families.


Assuntos
Imunidade Inata/genética , Imunidade Inata/imunologia , Interferons/imunologia , Nucleotidiltransferases/imunologia , Nucleotidiltransferases/metabolismo , Vírus/imunologia , Animais , Análise por Conglomerados , Vírus de DNA/imunologia , Vírus de DNA/patogenicidade , Citometria de Fluxo , Biblioteca Gênica , Fator Regulador 3 de Interferon/imunologia , Fator Regulador 3 de Interferon/metabolismo , Interferons/metabolismo , Proteínas de Membrana/metabolismo , Camundongos , Camundongos Knockout , Nucleotidiltransferases/deficiência , Nucleotidiltransferases/genética , Vírus de RNA/imunologia , Vírus de RNA/patogenicidade , Fator de Transcrição STAT1/metabolismo , Especificidade por Substrato , Vírus/classificação , Vírus/patogenicidade
15.
Microb Ecol ; 77(2): 502-512, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-29987529

RESUMO

The Pacific oyster, Crassostrea gigas, is a key commercial species that is cultivated globally. In recent years, disease outbreaks have heavily impacted C. gigas stocks worldwide, with many losses incurred during summer. A number of infectious agents have been associated with these summer mortality events, including viruses (particularly Ostreid herpesvirus 1, OsHV-1) and bacteria; however, cases where no known aetiological agent can be identified are common. In this study, we examined the microbiome of disease-affected and disease-unaffected C. gigas during a 2013-2014 summer mortality event in Port Stephens (Australia) where known oyster pathogens including OsHV-1 were not detected. The adductor muscle microbiomes of 70 C. gigas samples across 12 study sites in the Port Stephens estuary were characterised using 16S rRNA (V1-V3 region) amplicon sequencing, with the aim of comparing the influence of spatial location and disease state on the oyster microbiome. Spatial location was found to be a significant determinant of the disease-affected oyster microbiome. Furthermore, microbiome comparisons between disease states identified a significant increase in rare operational taxonomic units (OTUs) belonging to Vibrio harveyi and an unidentified member of the Vibrio genus in the disease-affected microbiome. This is indicative of a potential role of Vibrio species in oyster disease and supportive of previous culture-based examination of this mortality event.


Assuntos
Doenças dos Animais/microbiologia , Doenças dos Animais/mortalidade , Crassostrea/microbiologia , Microbiota , Ostreidae/microbiologia , Estações do Ano , Animais , Austrália , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Vírus de DNA/patogenicidade , DNA Bacteriano , Surtos de Doenças , Microbiota/genética , RNA Ribossômico 16S/genética , Vibrio/classificação , Vibrio/genética , Vibrio/isolamento & purificação , Vibrio/patogenicidade
16.
J Invertebr Pathol ; 162: 1-9, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30731071

RESUMO

The Caribbean spiny lobster Panulirus argus is susceptible to infection by Panulirus argus Virus 1 (PaV1), the only virus known to naturally infect any lobster species. However, P. argus is able to mitigate PaV1 transmission risk by avoiding infected individuals. P. argus may also be susceptible to another lethal virus, White Spot Syndrome Virus (WSSV). WSSV has not been documented in wild populations of spiny lobsters, but has been experimentally transmitted to six other lobster species from the genus Panulirus. Although WSSV has been detected intermittently in wild populations of shrimp in the Caribbean region, the risk to P. argus has not been evaluated. Potential emergence of the disease could result in fisheries losses and ecological disruption. To assess the risk to P. argus, we tested its susceptibility to WSSV via injection and waterborne transmission. We also tested whether healthy lobsters can detect and avoid conspecifics with qPCR-quantifiable WSSV infections. We found P. argus to be highly susceptible to WSSV via intramuscular injection, with mortality reaching 88% four weeks post inoculation. Panulirus argus was also susceptible to WSSV via waterborne transmission, but WSSV burden was low after four weeks via qPCR. Behavioral assays indicated that P. argus can detect and avoid conspecifics infected with WSSV and the avoidance response was strongest for the most heavily infected individuals - a response comparable to PaV1-infected conspecifics. Panulirus argus is the first spiny lobster found to be susceptible to WSSV in the Americas, but it is possible that a generalized avoidance response by healthy lobsters against infected conspecifics provides a behavioral defense and may reduce WSSV infection potential and prevalence. Preliminary evidence suggests that the infiltration of hemolymph constituents into the urine may be the source of the avoidance behavior and could therefore extend to other directly transmitted pathogens in spiny lobster populations preventing them from becoming common in their population.


Assuntos
Comportamento Animal , Suscetibilidade a Doenças/virologia , Palinuridae/virologia , Vírus da Síndrome da Mancha Branca 1/patogenicidade , Animais , Região do Caribe , Quimiotaxia/imunologia , Vírus de DNA/patogenicidade , Decápodes/virologia , Imunidade , Fatores de Risco , Alimentos Marinhos
17.
Proc Natl Acad Sci U S A ; 113(13): E1907-16, 2016 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-26984500

RESUMO

Marine viruses are the most abundant biological entities in the oceans shaping community structure and nutrient cycling. The interaction between the bloom-forming alga Emiliania huxleyi and its specific large dsDNA virus (EhV) is a major factor determining the fate of carbon in the ocean, thus serving as a key host-pathogen model system. The EhV genome encodes for a set of genes involved in the de novo sphingolipid biosynthesis, not reported in any viral genome to date. We combined detailed lipidomic and biochemical analyses to characterize the functional role of this virus-encoded pathway during lytic viral infection. We identified a major metabolic shift, mediated by differential substrate specificity of virus-encoded serine palmitoyltransferase, a key enzyme of sphingolipid biosynthesis. Consequently, unique viral glycosphingolipids, composed of unusual hydroxylated C17 sphingoid bases (t17:0) were highly enriched in the infected cells, and their synthesis was found to be essential for viral assembly. These findings uncover the biochemical bases of the virus-induced metabolic rewiring of the host sphingolipid biosynthesis during the chemical "arms race" in the ocean.


Assuntos
Vírus de DNA/patogenicidade , Haptófitas/virologia , Serina C-Palmitoiltransferase/metabolismo , Esfingolipídeos/biossíntese , Proteínas Virais/metabolismo , Vírus de DNA/metabolismo , Eutrofização , Regulação Viral da Expressão Gênica , Glicoesfingolipídeos/química , Glicoesfingolipídeos/metabolismo , Interações Hospedeiro-Patógeno , Hidroxilação , Doenças das Plantas/virologia , Serina C-Palmitoiltransferase/genética , Proteínas Virais/genética
18.
Rev Sci Tech ; 38(2): 491-509, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31866680

RESUMO

Mollusc farming is the third most productive aquaculture activity in the world, and the Pacific oyster (Crassostrea gigas) is one of the most important farmed species. Since 2008, mass mortalities in C. gigas due to ostreid herpesvirus 1 microvariants have challenged the viability of this industry in Europe, New Zealand and Australia. Ten years after the emergence of this disease, there is evidence that the industry has become consolidated into fewer, larger companies, with the displacement of small farming enterprises and loss of employment in coastal communities. Rather than seeking technical solutions, the industry has turned to compensatory production strategies, such as increasing the number of spat placed on farms, higher market prices for table oysters and direct marketing, which appear to have allowed profitability. Biosecurity policies and responses to outbreaks, including those from within the industry, have had unintended consequences for hatcheries and farmers in areas free of disease, mainly caused by restrictions on animal movements, and have not prevented global spread. There may be opportunities for better coordination of industry and government responses to epizootic disease emergence in aquaculture. There is certainly a need for increased adoption of technical advances from research, once these solutions have been adequately verified.


L'élevage de mollusques occupe le troisième rang mondial parmi les activités de l'aquaculture en termes de production ; l'une des principales espèces élevées est l'huître creuse (Crassostrea gigas). Depuis 2008, la rentabilité des élevages de C. gigas en Europe, en Nouvelle-Zélande et en Australie a été fortement compromise par une mortalité massive due à des microvariants du virus herpétique Ostreid herpesvirus 1. Dix ans après l'émergence de cette maladie, on observe une forte concentration du secteur autour d'entreprises moins nombreuses mais de plus grande envergure qui ont remplacé l'ancien tissu d'exploitations artisanales et occasionné un déclin de l'emploi dans les communautés littorales. Au lieu de rechercher des solutions techniques, le secteur a eu recours à des stratégies de compensation axées sur la production, par exemple en augmentant le nombre de naissains mis en place dans les fermes, en augmentant le prix des huîtres de consommation ou en développant la vente directe, stratégies dont l'impact sur la rentabilité semble avoir été positif. En revanche, les mesures de biosécurité mises en place et les réponses apportées aux foyers, y compris celles introduites par le secteur lui-même ont eu des conséquences imprévues pour les écloseries et les éleveurs des zones indemnes de maladie, principalement en raison des restrictions imposées aux transferts d'animaux, sans pour autant prévenir la propagation de la maladie à l'échelle mondiale. Une meilleure coordination des réponses sectorielles et publiques face à l'émergence des maladies épizootiques affectant l'aquaculture devrait être possible. Il sera également indispensable de recourir davantage aux avancées techniques mises au point par la recherche dès que ces solutions auront été dûment validées.


La producción de moluscos es la tercera actividad acuícola más productiva del mundo, y la ostra japonesa (o del Pacífico) (Crassostrea gigas) ocupa un lugar destacado entre las principales especies cultivadas. Desde 2008, la viabilidad de esta industria en Europa, Nueva Zelanda y Australia está amenazada por episodios de mortandad masiva de C. gigas causados por microvariantes del herpesvirus de los ostreidos 1 (ostreid herpesvirus 1). Diez años después de la aparición de la enfermedad, lo que se observa es que la industria se ha ido concentrando en unas pocas empresas de grandes dimensiones, que han desplazado a las pequeñas empresas ostrícolas y causado la pérdida de numerosos empleos en las comunidades costeras. En lugar de buscar soluciones técnicas, la industria ha optado más bien por estrategias de producción compensatorias (como aumentar el número de semillas de ostra por explotación, subir los precios de mercado de las ostras de mesa o recurrir a la comercialización directa) que parecen haber deparado rentabilidad. Las políticas de seguridad biológica y la respuesta a los brotes, incluida la del propio sector, han tenido consecuencias imprevistas para los viveros y acuicultores situados en zonas libres de la enfermedad, debido sobre todo a las restricciones impuestas a los desplazamientos de animales, sin que ello haya servido para impedir la diseminación mundial de esta patología. Puede haber margen para coordinar más eficazmente las respectivas respuestas de la industria y de los poderes públicos ante la aparición de enfermedades epizoóticas en la acuicultura. Lo que sin ninguna duda es necesario es incorporar en mayor medida los adelantos técnicos resultantes de la investigación, una vez contrastada debidamente cada solución.


Assuntos
Vírus de DNA/patogenicidade , Moluscos/virologia , Animais , Austrália , Crassostrea/virologia , Europa (Continente) , Interações Hospedeiro-Patógeno , Nova Zelândia
19.
J Gen Virol ; 99(5): 693-703, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29580370

RESUMO

The surveillance activities for abnormal bivalve mortality events in Italy include the diagnosis of ostreid herpesvirus type 1 (OsHV-1) in symptomatic oysters. OsHV-1-positive oysters (Crassostrea gigas) were used as a source for in vivo virus propagation and a virus-rich sample was selected to perform shotgun sequencing based on Illumina technology. Starting from this unpurified supernatant sample from gills and mantle, we generated 3.5 million reads (2×300 bp) and de novo assembled the whole genome of an Italian OsHV-1 microvariant (OsHV-1-PT). The OsHV-1-PT genome encodes 125 putative ORFs, 7 of which had not previously been predicted in other sequenced Malacoherpesviridae. Overall, OsHV-1-PT displays typical microvariant OsHV-1 genome features, while few polymorphisms (0.08 %) determine its uniqueness. As little is known about the genetic determinants of OsHV-1 virulence, comparing complete OsHV-1 genomes supports a better understanding of the virus pathogenicity and provides new insights into virus-host interactions.


Assuntos
Crassostrea/virologia , Vírus de DNA/classificação , Genoma Viral , Animais , Vírus de DNA/isolamento & purificação , Vírus de DNA/patogenicidade , DNA Viral/isolamento & purificação , Itália , Fases de Leitura Aberta , Filogenia , Polimorfismo Genético
20.
Eur J Immunol ; 47(5): 780-796, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28383780

RESUMO

Pathogens have developed a plethora of strategies to undermine host immune defenses in order to guarantee their survival. For large DNA viruses, these immune evasion mechanisms frequently rely on the expression of genes acquired from host genomes. Horizontally transferred genes include members of the immunoglobulin superfamily, whose products constitute the most diverse group of proteins of vertebrate genomes. Their promiscuous immunoglobulin domains, which comprise the building blocks of these molecules, are involved in a large variety of functions mediated by ligand-binding interactions. The flexible structural nature of the immunoglobulin domains makes them appealing targets for viral capture due to their capacity to generate high functional diversity. Here, we present an up-to-date review of immunoglobulin superfamily gene homologs encoded by herpesviruses, poxviruses, and adenoviruses, that include CD200, CD47, Fc receptors, interleukin-1 receptor 2, interleukin-18 binding protein, CD80, carcinoembryonic antigen-related cell adhesion molecules, and signaling lymphocyte activation molecules. We discuss their distinct structural attributes, binding properties, and functions, shaped by evolutionary pressures to disarm specific immune pathways. We include several novel genes identified from extensive genome database surveys. An understanding of the properties and modes of action of these viral proteins may guide the development of novel immune-modulatory therapeutic tools.


Assuntos
Vírus de DNA/genética , Vírus de DNA/patogenicidade , Evasão da Resposta Imune , Imunoglobulinas/imunologia , Proteínas Virais/imunologia , Adenovírus Humanos/genética , Adenovírus Humanos/imunologia , Adenovírus Humanos/patogenicidade , Animais , Antígenos CD/imunologia , Vírus de DNA/imunologia , Evolução Molecular , Transferência Genética Horizontal , Genes de Imunoglobulinas , Herpesviridae/genética , Herpesviridae/imunologia , Herpesviridae/patogenicidade , Humanos , Imunoglobulinas/genética , Imunoglobulinas/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/imunologia , Proteínas Virais/genética
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA