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  1 / 2012 MEDLINE  
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[PMID]:28822268
[Au] Autor:Mangale V; Marro BS; Plaisted WC; Walsh CM; Lane TE
[Ad] Endereço:Department of Pathology, Division of Microbiology & Immunology University of Utah, Salt Lake City, UT 84112, United States.
[Ti] Título:Neural precursor cells derived from induced pluripotent stem cells exhibit reduced susceptibility to infection with a neurotropic coronavirus.
[So] Source:Virology;511:49-55, 2017 Nov.
[Is] ISSN:1096-0341
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The present study examines the susceptibility of mouse induced pluripotent stem cell-derived neural precursor cells (iPSC-NPCs) to infection with the neurotropic JHM strain of mouse hepatitis virus (JHMV). Similar to NPCs derived from striatum of day 1 postnatal GFP-transgenic mice (GFP-NPCs), iPSC-derived NPCs (iPSC-NPCs) are able to differentiate into terminal neural cell types and express MHC class I and II in response to IFN-γ treatment. However, in contrast to postnatally-derived NPCs, iPSC-NPCs express low levels of carcinoembryonic antigen-cell adhesion molecule 1a (CEACAM1a), the surface receptor for JHMV, and are less susceptible to infection and virus-induced cytopathic effects. The relevance of this in terms of therapeutic application of NPCs resistant to viral infection is discussed.
[Mh] Termos MeSH primário: Diferenciação Celular
Células-Tronco Pluripotentes Induzidas/fisiologia
Vírus da Hepatite Murina/crescimento & desenvolvimento
Vírus da Hepatite Murina/imunologia
Células-Tronco Neurais/imunologia
Células-Tronco Neurais/virologia
[Mh] Termos MeSH secundário: Animais
Antígeno Carcinoembrionário/biossíntese
Expressão Gênica
Antígenos de Histocompatibilidade Classe I/biossíntese
Antígenos de Histocompatibilidade Classe II/biossíntese
Interferon gama/metabolismo
Camundongos
Camundongos Transgênicos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carcinoembryonic Antigen); 0 (Ceacam1 protein, mouse); 0 (Histocompatibility Antigens Class I); 0 (Histocompatibility Antigens Class II); 82115-62-6 (Interferon-gamma)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171010
[Lr] Data última revisão:
171010
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170820
[St] Status:MEDLINE


  2 / 2012 MEDLINE  
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[PMID]:28566289
[Au] Autor:Basu R; Bose A; Thomas D; Das Sarma J
[Ad] Endereço:From the Department of Biological Sciences, Indian Institute of Science Education and Research Kolkata, Mohanpur-741246, India.
[Ti] Título:Microtubule-assisted altered trafficking of astrocytic gap junction protein connexin 43 is associated with depletion of connexin 47 during mouse hepatitis virus infection.
[So] Source:J Biol Chem;292(36):14747-14763, 2017 Sep 08.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Gap junctions (GJs) are important for maintenance of CNS homeostasis. GJ proteins, connexin 43 (Cx43) and connexin 47 (Cx47), play a crucial role in production and maintenance of CNS myelin. Cx43 is mainly expressed by astrocytes in the CNS and forms gap junction intercellular communications between astrocytes-astrocytes (Cx43-Cx43) and between astrocytes-oligodendrocytes (Cx43-Cx47). Mutations of these connexin (Cx) proteins cause dysmyelinating diseases in humans. Previously, it has been shown that Cx43 localization and expression is altered due to mouse hepatitis virus (MHV)-A59 infection both and ; however, its mechanism and association with loss of myelin protein was not elaborated. Thus, we explored potential mechanisms by which MHV-A59 infection alters Cx43 localization and examined the effects of viral infection on Cx47 expression and its association with loss of the myelin marker proteolipid protein. Immunofluorescence and total internal reflection fluorescence microscopy confirmed that MHV-A59 used microtubules (MTs) as a conduit to reach the cell surface and restricted MT-mediated Cx43 delivery to the cell membrane. Co-immunoprecipitation experiments demonstrated that Cx43-ß-tubulin molecular interaction was depleted due to protein-protein interaction between viral particles and MTs. During acute MHV-A59 infection, oligodendrocytic Cx47, which is mainly stabilized by Cx43 , was down-regulated, and its characteristic staining remained disrupted even at chronic phase. The loss of Cx47 was associated with loss of proteolipid protein at the chronic stage of MHV-A59 infection.
[Mh] Termos MeSH primário: Astrócitos/metabolismo
Conexina 43/metabolismo
Conexinas/metabolismo
Junções Comunicantes/metabolismo
Hepatite/metabolismo
Microtúbulos/metabolismo
Vírus da Hepatite Murina/fisiologia
[Mh] Termos MeSH secundário: Animais
Astrócitos/citologia
Conexinas/deficiência
Hepatite/virologia
Camundongos
Camundongos Endogâmicos C57BL
Vírus da Hepatite Murina/isolamento & purificação
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Connexin 43); 0 (Connexins); 0 (connexin 47)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170602
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.786491


  3 / 2012 MEDLINE  
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[PMID]:28494352
[Au] Autor:Yu H; Liu Y; Huang J; Wang H; Yan W; Xi D; Shen G; Luo X; Ning Q
[Ad] Endereço:Department of Infectious Disease, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
[Ti] Título:IL-33 protects murine viral fulminant hepatitis by targeting coagulation hallmark protein FGL2/fibroleukin expression.
[So] Source:Mol Immunol;87:171-179, 2017 Jul.
[Is] ISSN:1872-9142
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Fulminant hepatitis (FH) is characterized by rapid liver failure and high mortality. The pathogenesis of viral FH includes virus-induced immune activation, inflammation, and subsequent hepatic apoptosis and necrosis. However, the mechanisms that underlie FH progression are unclear. IL-33 is a member of the IL-1-related cytokines, considered to be an "alarmin" that participates in various diseases, but its precise role in the coagulation of FH is not very clear. In our study, we found that IL-33 is significantly elevated in mice infected with murine hepatitis virus strain 3 (MHV-3). This is accompanied by an increase in pro-coagulant fibrinogen-like protein 2 (FGL2) in the liver. Previous studies have suggested that an increase in FGL2 is diagnostic of FH and liver necrosis, and animals with no FGL2 had better survivorship during FH. Our studies showed that IL-33 administration in a MHV-3 infection promoted survival during FH, with a significant reduction in FGL2 expression and liver inflammation. In vitro IL-33 treatment abrogated MHV-3 and IFN-γ induced FGL2 expression in RAW264.7 and THP-1 cells, respectively. In conclusion, our research suggests that IL-33 protects against viral fulminant hepatitis in mice by antagonizing expression of the pro-coagulant protein FGL2.
[Mh] Termos MeSH primário: Coagulação Sanguínea/fisiologia
Fibrinogênio/metabolismo
Hepatite Viral Animal/metabolismo
Interleucina-33/metabolismo
Vírus da Hepatite Murina/metabolismo
[Mh] Termos MeSH secundário: Animais
Apoptose/fisiologia
Feminino
Inflamação/metabolismo
Inflamação/virologia
Interferon gama/metabolismo
Interleucina-1/metabolismo
Fígado/metabolismo
Fígado/virologia
Camundongos
Camundongos Endogâmicos BALB C
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Fgl2 protein, mouse); 0 (Il33 protein, mouse); 0 (Interleukin-1); 0 (Interleukin-33); 82115-62-6 (Interferon-gamma); 9001-32-5 (Fibrinogen)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170912
[Lr] Data última revisão:
170912
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170512
[St] Status:MEDLINE


  4 / 2012 MEDLINE  
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[PMID]:28438633
[Au] Autor:Daczkowski CM; Dzimianski JV; Clasman JR; Goodwin O; Mesecar AD; Pegan SD
[Ad] Endereço:Department of Pharmaceutical and Biomedical Sciences, University of Georgia, Athens, GA 30602, USA.
[Ti] Título:Structural Insights into the Interaction of Coronavirus Papain-Like Proteases and Interferon-Stimulated Gene Product 15 from Different Species.
[So] Source:J Mol Biol;429(11):1661-1683, 2017 Jun 02.
[Is] ISSN:1089-8638
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) encode multifunctional papain-like proteases (PLPs) that have the ability to process the viral polyprotein to facilitate RNA replication and antagonize the host innate immune response. The latter function involves reversing the post-translational modification of cellular proteins conjugated with either ubiquitin (Ub) or Ub-like interferon-stimulated gene product 15 (ISG15). Ub is known to be highly conserved among eukaryotes, but surprisingly, ISG15 is highly divergent among animals. The ramifications of this sequence divergence to the recognition of ISG15 by coronavirus PLPs at a structural and biochemical level are poorly understood. Therefore, the activity of PLPs from SARS-CoV, MERS-CoV, and mouse hepatitis virus was evaluated against seven ISG15s originating from an assortment of animal species susceptible, and not, to certain coronavirus infections. Excitingly, our kinetic, thermodynamic, and structural analysis revealed an array of different preferences among PLPs. Included in these studies is the first insight into a coronavirus PLP's interface with ISG15 via SARS-CoV PLpro in complex with the principle binding domain of human ISG15 (hISG15) and mouse ISG15s (mISG15s). The first X-ray structure of the full-length mISG15 protein is also reported and highlights a unique, twisted hinge region of ISG15 that is not conserved in hISG15, suggesting a potential role in differential recognition. Taken together, this new information provides a structural and biochemical understanding of the distinct specificities among coronavirus PLPs observed and addresses a critical gap of how PLPs can interact with ISG15s from a wide variety of species.
[Mh] Termos MeSH primário: Cisteína Endopeptidases/química
Cisteína Endopeptidases/metabolismo
Coronavírus da Síndrome Respiratória do Oriente Médio/enzimologia
Vírus da Hepatite Murina/enzimologia
Vírus da SARS/enzimologia
Ubiquitinas/química
Ubiquitinas/metabolismo
Proteínas Virais/química
Proteínas Virais/metabolismo
[Mh] Termos MeSH secundário: Animais
Cristalografia por Raios X
Seres Humanos
Cinética
Camundongos
Ligação Proteica
Conformação Proteica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Ubiquitins); 0 (Viral Proteins); EC 3.4.22.- (Cysteine Endopeptidases); EC 3.4.22.28 (3C proteases)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171011
[Lr] Data última revisão:
171011
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170426
[St] Status:MEDLINE


  5 / 2012 MEDLINE  
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[PMID]:28148786
[Au] Autor:Phillips JM; Gallagher T; Weiss SR
[Ad] Endereço:Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA jphil@upenn.edu.
[Ti] Título:Neurovirulent Murine Coronavirus JHM.SD Uses Cellular Zinc Metalloproteases for Virus Entry and Cell-Cell Fusion.
[So] Source:J Virol;91(8), 2017 Apr 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The coronavirus (CoV) S protein requires cleavage by host cell proteases to mediate virus-cell and cell-cell fusion. Many strains of the murine coronavirus mouse hepatitis virus (MHV) have distinct, S-dependent organ and tissue tropisms despite using a common receptor, suggesting that they employ different cellular proteases for fusion. In support of this hypothesis, we found that inhibition of endosomal acidification only modestly decreased entry, and overexpression of the cell surface protease TMPRSS2 greatly enhanced entry, of the highly neurovirulent MHV strain JHM.SD relative to their effects on the reference strain, A59. However, TMPRSS2 overexpression decreased MHV structural protein expression, release of infectious particles, and syncytium formation, and endogenous serine protease activity did not contribute greatly to infection. We therefore investigated the importance of other classes of cellular proteases and found that inhibition of matrix metalloproteinase (MMP)- and a disintegrin and metalloprotease (ADAM)-family zinc metalloproteases markedly decreased both entry and cell-cell fusion. Suppression of virus by metalloprotease inhibition varied among tested cell lines and MHV S proteins, suggesting a role for metalloprotease use in strain-dependent tropism. We conclude that zinc metalloproteases must be considered potential contributors to coronavirus fusion. The family includes viruses that cause two emerging diseases of humans, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS), as well as a number of important animal pathogens. Because coronaviruses depend on host protease-mediated cleavage of their S proteins for entry, a number of protease inhibitors have been proposed as antiviral agents. However, it is unclear which proteases mediate infection. For example, SARS-CoV infection of cultured cells depends on endosomal acid pH-dependent proteases rather than on the cell surface acid pH-independent serine protease TMPRSS2, but Zhou et al. (Antiviral Res 116:76-84, 2015, doi:10.1016/j.antiviral.2015.01.011) found that a serine protease inhibitor was more protective than a cathepsin inhibitor in SARS-CoV-infected mice. This paper explores the contributions of endosomal acidification and various proteases to coronavirus infection and identifies an unexpected class of proteases, the matrix metalloproteinase and ADAM families, as potential targets for anticoronavirus therapy.
[Mh] Termos MeSH primário: Fusão Celular
Interações Hospedeiro-Patógeno
Metaloproteases/metabolismo
Vírus da Hepatite Murina/fisiologia
Internalização do Vírus
[Mh] Termos MeSH secundário: Animais
Camundongos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 3.4.- (Metalloproteases)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170929
[Lr] Data última revisão:
170929
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170203
[St] Status:MEDLINE


  6 / 2012 MEDLINE  
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[PMID]:28143984
[Au] Autor:Athmer J; Fehr AR; Grunewald M; Smith EC; Denison MR; Perlman S
[Ad] Endereço:Department of Microbiology, University of Iowa, Iowa City, Iowa, USA.
[Ti] Título:In Situ Tagged nsp15 Reveals Interactions with Coronavirus Replication/Transcription Complex-Associated Proteins.
[So] Source:MBio;8(1), 2017 Jan 31.
[Is] ISSN:2150-7511
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Coronavirus (CoV) replication and transcription are carried out in close proximity to restructured endoplasmic reticulum (ER) membranes in replication/transcription complexes (RTC). Many of the CoV nonstructural proteins (nsps) are required for RTC function; however, not all of their functions are known. nsp15 contains an endoribonuclease domain that is conserved in the CoV family. While the enzymatic activity and crystal structure of nsp15 are well defined, its role in replication remains elusive. nsp15 localizes to sites of RNA replication, but whether it acts independently or requires additional interactions for its function remains unknown. To begin to address these questions, we created an in situ tagged form of nsp15 using the prototypic CoV, mouse hepatitis virus (MHV). In MHV, nsp15 contains the genomic RNA packaging signal (P/S), a 95-bp RNA stem-loop structure that is not required for viral replication or nsp15 function. Utilizing this knowledge, we constructed an internal hemagglutinin (HA) tag that replaced the P/S. We found that nsp15-HA was localized to discrete perinuclear puncta and strongly colocalized with nsp8 and nsp12, both well-defined members of the RTC, but not the membrane (M) protein, involved in virus assembly. Finally, we found that nsp15 interacted with RTC-associated proteins nsp8 and nsp12 during infection, and this interaction was RNA independent. From this, we conclude that nsp15 localizes and interacts with CoV proteins in the RTC, suggesting it plays a direct or indirect role in virus replication. Furthermore, the use of in situ epitope tags could be used to determine novel nsp-nsp interactions in coronaviruses. IMPORTANCE: Despite structural and biochemical data demonstrating that the coronavirus nsp15 protein contains an endoribonuclease domain, its precise function during coronavirus infection remains unknown. In this work, we created a novel in situ tagged form of nsp15 to study interactions and localization during infection. This in situ tag was tolerated by MHV and did not affect viral replication. Utilizing this tag, we established that nsp15 localized to sites of replication but not sites of assembly throughout infection. Furthermore, we found that nsp15 interacted with the putative viral primase nsp8 and polymerase nsp12 during CoV infection. The strong association of nsp15 with replication complexes and interactions with replicative CoV enzymes suggest nsp15 is involved in CoV replication. These data and tools developed in this study help elucidate the function of nsp15 during infection and may be used to uncover other novel viral protein interactions.
[Mh] Termos MeSH primário: Vírus da Hepatite Murina/fisiologia
Multimerização Proteica
Transcrição Genética
Proteínas não Estruturais Virais/metabolismo
Replicação Viral
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Seres Humanos
Vírus da Hepatite Murina/genética
Ligação Proteica
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Viral Nonstructural Proteins)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171109
[Lr] Data última revisão:
171109
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170202
[St] Status:MEDLINE


  7 / 2012 MEDLINE  
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[PMID]:28035001
[Au] Autor:Peng G; Yang Y; Pasquarella JR; Xu L; Qian Z; Holmes KV; Li F
[Ad] Endereço:From the Department of Pharmacology, University of Minnesota Medical School, Minneapolis, Minnesota 55455.
[Ti] Título:Structural and Molecular Evidence Suggesting Coronavirus-driven Evolution of Mouse Receptor.
[So] Source:J Biol Chem;292(6):2174-2181, 2017 Feb 10.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Hosts and pathogens are locked in an evolutionary arms race. To infect mice, mouse hepatitis coronavirus (MHV) has evolved to recognize mouse CEACAM1a (mCEACAM1a) as its receptor. To elude MHV infections, mice may have evolved a variant allele from the gene, called , producing mCEACAM1b, which is a much poorer MHV receptor than mCEACAM1a. Previous studies showed that sequence differences between mCEACAM1a and mCEACAM1b in a critical MHV-binding CC' loop partially account for the low receptor activity of mCEACAM1b, but detailed structural and molecular mechanisms for the differential MHV receptor activities of mCEACAM1a and mCEACAM1b remained elusive. Here we have determined the crystal structure of mCEACAM1b and identified the structural differences and additional residue differences between mCEACAM1a and mCEACAM1b that affect MHV binding and entry. These differences include conformational alterations of the CC' loop as well as residue variations in other MHV-binding regions, including ß-strands C' and C'' and loop C'C''. Using pseudovirus entry and protein-protein binding assays, we show that substituting the structural and residue features from mCEACAM1b into mCEACAM1a reduced the viral receptor activity of mCEACAM1a, whereas substituting the reverse changes from mCEACAM1a into mCEACAM1b increased the viral receptor activity of mCEACAM1b. These results elucidate the detailed molecular mechanism for how mice may have kept pace in the evolutionary arms race with MHV by undergoing structural and residue changes in the MHV receptor, providing insight into this possible example of pathogen-driven evolution of a host receptor protein.
[Mh] Termos MeSH primário: Antígeno Carcinoembrionário/metabolismo
Vírus da Hepatite Murina/metabolismo
Receptores Virais/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Sítios de Ligação
Antígeno Carcinoembrionário/química
Cristalografia por Raios X
Fusão de Membrana
Camundongos
Vírus da Hepatite Murina/fisiologia
Mutação
Conformação Proteica
Receptores Virais/química
Homologia de Sequência de Aminoácidos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Carcinoembryonic Antigen); 0 (Ceacam1 protein, mouse); 0 (Receptors, Virus)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170704
[Lr] Data última revisão:
170704
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161231
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M116.764266


  8 / 2012 MEDLINE  
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[PMID]:28003490
[Au] Autor:Goldstein SA; Thornbrough JM; Zhang R; Jha BK; Li Y; Elliott R; Quiroz-Figueroa K; Chen AI; Silverman RH; Weiss SR
[Ad] Endereço:Department of Microbiology, Perlman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania, USA.
[Ti] Título:Lineage A Betacoronavirus NS2 Proteins and the Homologous Torovirus Berne pp1a Carboxy-Terminal Domain Are Phosphodiesterases That Antagonize Activation of RNase L.
[So] Source:J Virol;91(5), 2017 Mar 01.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Viruses in the family , within the order , are etiologic agents of a range of human and animal diseases, including both mild and severe respiratory diseases in humans. These viruses encode conserved replicase and structural proteins as well as more diverse accessory proteins, encoded in the 3' ends of their genomes, that often act as host cell antagonists. We previously showed that 2',5'-phosphodiesterases (2',5'-PDEs) encoded by the prototypical , mouse hepatitis virus (MHV), and by Middle East respiratory syndrome-associated coronavirus antagonize the oligoadenylate-RNase L (OAS-RNase L) pathway. Here we report that additional coronavirus superfamily members, including lineage A betacoronaviruses and toroviruses infecting both humans and animals, encode 2',5'-PDEs capable of antagonizing RNase L. We used a chimeric MHV system (MHV ) in which exogenous PDEs were expressed from an MHV backbone lacking the gene for a functional NS2 protein, the endogenous RNase L antagonist. With this system, we found that 2',5'-PDEs encoded by the human coronavirus HCoV-OC43 (OC43; an agent of the common cold), human enteric coronavirus (HECoV), equine coronavirus (ECoV), and equine torovirus Berne (BEV) are enzymatically active, rescue replication of MHV in bone marrow-derived macrophages, and inhibit RNase L-mediated rRNA degradation in these cells. Additionally, PDEs encoded by OC43 and BEV rescue MHV replication and restore pathogenesis in wild-type (WT) B6 mice. This finding expands the range of viruses known to encode antagonists of the potent OAS-RNase L antiviral pathway, highlighting its importance in a range of species as well as the selective pressures exerted on viruses to antagonize it. Viruses in the family include important human and animal pathogens, including the recently emerged viruses severe acute respiratory syndrome-associated coronavirus (SARS-CoV) and Middle East respiratory syndrome-associated coronavirus (MERS-CoV). We showed previously that two viruses within the genus , mouse hepatitis virus (MHV) and MERS-CoV, encode 2',5'-phosphodiesterases (2',5'-PDEs) that antagonize the OAS-RNase L pathway, and we report here that these proteins are furthermore conserved among additional coronavirus superfamily members, including lineage A betacoronaviruses and toroviruses, suggesting that they may play critical roles in pathogenesis. As there are no licensed vaccines or effective antivirals against human coronaviruses and few against those infecting animals, identifying viral proteins contributing to virulence can inform therapeutic development. Thus, this work demonstrates that a potent antagonist of host antiviral defenses is encoded by multiple and diverse viruses within the family , presenting a possible broad-spectrum therapeutic target.
[Mh] Termos MeSH primário: Endorribonucleases/metabolismo
Coronavírus da Síndrome Respiratória do Oriente Médio/enzimologia
Vírus da Hepatite Murina/enzimologia
Diester Fosfórico Hidrolases/fisiologia
Torovirus/enzimologia
Proteínas não Estruturais Virais/fisiologia
[Mh] Termos MeSH secundário: Nucleotídeos de Adenina/química
Sequência de Aminoácidos
Animais
Domínio Catalítico
Linhagem Celular
Sequência Conservada
Cricetinae
Ativação Enzimática
Macrófagos/virologia
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Oligorribonucleotídeos/química
Diester Fosfórico Hidrolases/química
Proteínas não Estruturais Virais/química
Replicação Viral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adenine Nucleotides); 0 (Oligoribonucleotides); 0 (Viral Nonstructural Proteins); 61172-40-5 (2',5'-oligoadenylate); EC 3.1.- (Endoribonucleases); EC 3.1.26.- (2-5A-dependent ribonuclease); EC 3.1.4.- (Phosphoric Diester Hydrolases)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170814
[Lr] Data última revisão:
170814
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161223
[St] Status:MEDLINE


  9 / 2012 MEDLINE  
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[PMID]:27798617
[Au] Autor:Gil-Cruz C; Perez-Shibayama C; Onder L; Chai Q; Cupovic J; Cheng HW; Novkovic M; Lang PA; Geuking MB; McCoy KD; Abe S; Cui G; Ikuta K; Scandella E; Ludewig B
[Ad] Endereço:Institute of Immunobiology, Kantonsspital St. Gallen, St. Gallen, Switzerland.
[Ti] Título:Fibroblastic reticular cells regulate intestinal inflammation via IL-15-mediated control of group 1 ILCs.
[So] Source:Nat Immunol;17(12):1388-1396, 2016 Dec.
[Is] ISSN:1529-2916
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Fibroblastic reticular cells (FRCs) of secondary lymphoid organs form distinct niches for interaction with hematopoietic cells. We found here that production of the cytokine IL-15 by FRCs was essential for the maintenance of group 1 innate lymphoid cells (ILCs) in Peyer's patches and mesenteric lymph nodes. Moreover, FRC-specific ablation of the innate immunological sensing adaptor MyD88 unleashed IL-15 production by FRCs during infection with an enteropathogenic virus, which led to hyperactivation of group 1 ILCs and substantially altered the differentiation of helper T cells. Accelerated clearance of virus by group 1 ILCs precipitated severe intestinal inflammatory disease with commensal dysbiosis, loss of intestinal barrier function and diminished resistance to colonization. In sum, FRCs act as an 'on-demand' immunological 'rheostat' by restraining activation of group 1 ILCs and thereby preventing immunopathological damage in the intestine.
[Mh] Termos MeSH primário: Citrobacter rodentium/imunologia
Infecções por Coronavirus/imunologia
Infecções por Enterobacteriaceae/imunologia
Fibroblastos/imunologia
Interleucina-15/metabolismo
Linfócitos/imunologia
Vírus da Hepatite Murina/imunologia
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Imunidade Inata
Linfonodos/patologia
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Fator 88 de Diferenciação Mieloide/genética
Fator 88 de Diferenciação Mieloide/metabolismo
Nódulos Linfáticos Agregados/patologia
Células Th1/imunologia
Receptor 7 Toll-Like/genética
Receptor 7 Toll-Like/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Interleukin-15); 0 (Myeloid Differentiation Factor 88); 0 (TLR7 protein, human); 0 (Toll-Like Receptor 7)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170719
[Lr] Data última revisão:
170719
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161101
[St] Status:MEDLINE
[do] DOI:10.1038/ni.3566


  10 / 2012 MEDLINE  
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[PMID]:27558415
[Au] Autor:Li Y; Weiss SR
[Ad] Endereço:Department of Microbiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
[Ti] Título:Antagonism of RNase L Is Required for Murine Coronavirus Replication in Kupffer Cells and Liver Sinusoidal Endothelial Cells but Not in Hepatocytes.
[So] Source:J Virol;90(21):9826-9832, 2016 Nov 01.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Mouse hepatitis virus strain A59 infection of mice is a useful tool for studying virus-host interaction during hepatitis development. The NS2 mutant is attenuated in liver replication due to loss of phosphodiesterase activity, which the wild-type (WT) virus uses to block the 2',5'-oligoadenylate synthetase (OAS)-RNase L (RNase L) antiviral pathway. The activation of RNase L by NS2 is cell type dependent and correlates with high basal expression levels of OAS, as found in myeloid cells. We tested the hypothesis that the resident liver macrophages, Kupffer cells (KC), represent the cell type most likely to restrict NS2 and prevent hepatitis. As found previously, A59 and NS2 replicate similarly in hepatocytes and neither activates RNase L, as assessed by an rRNA degradation assay. In contrast, in KC, A59 exhibited a 100-fold-higher titer than NS2 and NS2 induced rRNA degradation. Interestingly, in liver sinusoidal endothelial cells (LSEC), the cells that form a barrier between blood and liver parenchymal cells, NS2 activates RNase L, which limits viral replication. Similar growth kinetics were observed for the two viruses in KC and LSEC from RNase L mice, demonstrating that both use RNase L to limit NS2 replication. Depletion of KC by gadolinium(III) chloride or of LSEC by cyclophosphamide partially restores liver replication of NS2 , leading to hepatitis. Thus, during mouse hepatitis virus (MHV) infection, hepatitis, which damages the parenchyma, is prevented by RNase L activity in both KC and LSEC but not in hepatocytes. This may be explained by the undetectable levels of RNase L as well as by the OASs expressed in hepatocytes. IMPORTANCE: Mouse hepatitis virus infection of mice provides a useful tool for studying virus-host interactions during hepatitis development. The NS2 mutant is attenuated in liver replication due to loss of phosphodiesterase activity, by which the wild-type virus blocks the potent OAS-RNase L antiviral pathway. RNase L activation by NS2 is cell type dependent and correlates with high basal expression levels of OAS, as found in myeloid cells. We showed that the hepatocytes that comprise the liver parenchyma do not activate RNase L when infected with NS2 or restrict replication. However, both Kupffer cells (KC) (i.e., the liver-resident macrophages) and the liver sinusoidal endothelial cells (LSEC) which line the sinusoids activate RNase L in response to NS2 These data suggest that KC and LSEC prevent viral spread into the parenchyma, preventing hepatitis. Furthermore, hepatocytes express undetectable levels of OASs and RNase L, which likely explains the lack of RNase L activation during NS2 infection.
[Mh] Termos MeSH primário: Coronavirus/genética
Coronavirus/metabolismo
Endorribonucleases/metabolismo
Células Endoteliais/virologia
Macrófagos do Fígado/virologia
Fígado/virologia
Replicação Viral/fisiologia
[Mh] Termos MeSH secundário: 2',5'-Oligoadenilato Sintetase/metabolismo
Nucleotídeos de Adenina/metabolismo
Animais
Células Cultivadas
Replicação do DNA/fisiologia
Hepatócitos/virologia
Interações Hospedeiro-Patógeno/fisiologia
Camundongos
Camundongos Endogâmicos C57BL
Vírus da Hepatite Murina/metabolismo
Células Mieloides/virologia
Oligorribonucleotídeos/metabolismo
Proteínas não Estruturais Virais/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adenine Nucleotides); 0 (Oligoribonucleotides); 0 (Viral Nonstructural Proteins); 61172-40-5 (2',5'-oligoadenylate); EC 2.7.7.84 (2',5'-Oligoadenylate Synthetase); EC 3.1.- (Endoribonucleases); EC 3.1.26.- (2-5A-dependent ribonuclease)
[Em] Mês de entrada:1705
[Cu] Atualização por classe:170505
[Lr] Data última revisão:
170505
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:160826
[St] Status:MEDLINE



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